Index

A myopathy, 18 ABD (actin-binding domain), 69 intranuclear rod myopathy, 18 Aβ (amyloidbeta ), 192 nemaline myopathy, 18, 23 ABP (actin-binding protein), 1, 6, 229 ACTA1 myopathy mutations, molecular ABP activity, in cancer cells effects of, 23–26 membrane lipids and upstream ACTC. See Cardiomyopathy enzymes, 257 ACTG1 (Gamma actin) mutation, 26 phosphorylation, 258 Actin scaffolding , 257 autoantigenicity of. See upstream master regulators, 257 Autoantigenicity of actin ABPs, classes of, 278 driving cell migration, 230 ABPs, defects of epitopes of, 58 α-, 285 in long-distance virus transport, , 285 307 , 286 mutations, 16 nonmuscle , 286 myopathy, 18 , 285 polymerization (see Actin assembly AC (ADF/cofilin) proteins, 83 modulation and polymerization) AC, regulation of, 93 scaffolds, 299, 300 14-3-3 proteins, 98 treadmilling, 85 actin-interacting protein 1, 100 Actin and ABP in cancer pH, 97 cell migration, 230, 235 phosphatidylinositol-phosphate deregulation within actin system. binding, 98 (see Actin system deregulation in phosphorylation, 95 cancer cells; Gene mutation , 101 and deregulated gene transcription; Srv2/CAP, 100 ABP activity, in cancer cells) tropomyosins, 98 matrix and host cells, 235 AC–actin interaction, biochemical migratory modes, 224 analysis of, 90–92 Actin and ABP in failure AC–actin rod formation, 130 cardiac α-actin mutations (see Acanthamoeba actobindin, 219 Cardiomyopathies for cardiac Acelyl choline receptor (myasthenia α-actin mutations) gravis), 60 LIM proteins (see LIM proteins and ACTA1 mutants heart failure)

335 336 Index

Actin and ABP in heart failure Actin-based motors, 300 (continued ) Actin-binding domains (ABDs), 69 nonsarcomeric ABP mutations, Actin-binding drugs, 37 327–328 for cancer cells, 38, 43–46 pathophysiology of heart failure, 318 in diseases, 38 sarcomeric ABP mutations, 326–327 endothelial cells, 38 Actin assembly mode of action, 38 activation, 6 structures of, 40 cell turnover, 8–9 transendothelial transport, 39 critical concentration, 5 Actin-binding protein function and elongation and annealing, 7–8 disease pathology gene expression, 9–10 actin assembly modulation (see Actin nucleation, 7 assembly modulation and overview, 84 polymerization) regulation, 84 actin filament bundles disorder Actin assembly, modulation and (see Actin filament bundles and polymerization networks, mutations in) actin dynamics, regulation of, 67 actin-ECM crosslinking, 73–74 pathogenic bacteria and viruses, 66 actin-membrane disruption, 73–74 Actin filament bundles and networks, actomyosin-based contractility mutations in (see Actomyosin-based crosslinking proteins, 69, 70 contractility, disruption of) deafness, 71 defects in cell motility, 68–69 filamin-related diseases, 72 Actin-binding proteins. See ABP muscular dystrophy, 72 Actin-depolymerizing factor. See ADF renal disorders, 72 Actin-dynamizing cycle, 94 Actin genetic diseases, 16 Actin-ECM crosslinking, 73 actin ubiquitination, 28 Actin-interacting protein 1, 100 cardiomyopathy (ACTC), 17 Actin-interacting toxins, 300 congenital skeletal myopathies Actin-like proteins (ALP), 309 (ACTA1), 18 Actin-membrane, disruption of, 73 gamma actin (ACTG1) gene Actin–myosin motility chamber, 60, 61 mutations and mutations, 26 Actin–myosin motor system, 60 Actin monomer pool (expression Actinopathy, 23, 24, 26 regulatory), 90 Actin-stabilizer phalloidin, 44 Actin monomer sequestering protein, Actin–Tβ4 complex, 222 101, 233 Actomyosin ATPase activity, 60 Actin system deregulation, in cancer Actomyosin contractile ring, 102 cells Actomyosin motility assay, 25 actin expression, 241 Actomyosin-based contractility, altered regulation of ABP activity, disruption of. See also nonmuscle 256 mutation deregulated gene transcription, 242 causing diseases muscle myosin, gene mutation, 242 74, 75 Actin ubiquitination, 28–29 nonmuscle myosins,75 Actin, nuclear import of regulatory proteins, 74, 75 chromatin remodeling, 107 Acute respiratory distress syndrome transcription, 107 (ARDS), 193 Actin, polymerization of, 5, 6 Adaptive immune system, 51 Index 337

ADF (actin-depolymerizing factor), 83 ADF/cofilin expression ADF null mice, 110 actin monomer pool, 90 ADF/cofilin (AC) proteins, 83 developmental and issue expression ADF/cofilin (developmental disorders) pattern, 88 corneal disease, 111 mammalian genes, 88 corticobasal degeneration, 120 ADF/cofilin family, of actin assembly dementias, 120 regulatory proteins dendritic spine development, 116 in angiogenesis, 148 dendritic spine dysgenesis and identification and naming, 86 synaptic defects, 116 in disease, 111 gametogenesis, 113 muscle-specific cofilin, 86 long-term depression (LTD), 119 nonmuscle cofilin, 86 long-term potentiation (LTP), 119 structure of ADF/cofilin, 87 memory, learning, mental Illness, 123 ADF/cofilin knockout, in neural crest disorders, 113 nonmammalian system Williams syndrome, 120 caenorhabditis elegans, 109 X-linked nonsyndromic mental dictyostelium discoideum, 109 retardation, 122 saccharomyces cerevisiae, 109 ADF/cofilin, roles in diseases ADF/cofilin knockouts, in mammals AC–Actin interaction, 90–93 ADF null mice, 110 actin assembly regulatory proteins, ADF/cofilin expression silencing, 86–88 110 actin assembly, 84–85 cofilin-1 null mice, 110 ADF/cofilin expression, 88–90 cofilin-2, 110 bacterial invasion and pathogenesis, early developmental disorders, 111 151 ADF/cofilins deficiency, 111 cancer, 138–149 ADP-actin, 7 cell aging, 150 AIH. See Autoimmune hepatitis cell polarity and polarized migration, AJC (apical junctional complex), 154 102 ALK (anaplastic lymphoma kinase) cellular senescence, 150 receptor, 244 cytokinesis, 101 α-actinin, 285, 327 developmental disorders, 111–123 α-actinin-4 mutations, 72, 73 diseases based on inclusions, 125–135 α-cardiac muscle actin, 56 diseases of mRNA delivery and α-smooth muscle actin, 56 translation, 123–125 α-striated muscle actin, 56 function defining roles in diseases, α-, 21, 22, 327 101–108 α-actinin binding, 27 gene knockout in mammals, 110–111 α-skeletal actin, 20 gene knockout in nonmammalian ALS (Amyotrophic lateral sclerosis), systems, 109–110 126, 127 golgi tubule formation, 105 Alzheimer’s disease, 128–131, 192, 210 immune diseases, 136–138 Amellipodia, 148 inflammation, 149–150 Amoeboid, 234 mitochondrial-dependent apoptosis, Amoeboid–mesemchymal transition. 106 See AMT musculoskeletal diseases, 135–136 AMT (amoeboid–mesemchymal nuclear import of actin, 107 transition), 238 regulation of AC, 93–101 Amyloid β (Aβ), 128, 129, 192 338 Index

Amyloid precursor protein (APP), immunity and autoimmunity, 50 128, 307 immunogenic stimulus for Amyloidosis, 190, 192 anticytoskeletal antibodies, 57 Amyotrophic lateral sclerosis (ALS), innate and adaptive immunity, 51 126, 127 smooth muscle antibody, 53 ANA (antinuclear antibody), 53 tolerance and autoimmunity, 52 Anaplastic lymphoma kinase (ALK) Autoimmunity, 50, 52 receptor, 244 Autosomal-dominant Larsen syndrome, Angiogenesis, 147 286 inhibitors, 148 Avian leukosis virus, 303 and Tβ4 (Thymosin β4), 222 Angiogenic switch, 148 B Annealing process, 7 Bacterial invasion and pathogenesis Anterograde transport, 306 bacterial uptake, 151 Antiactin serum, 57 bacterial motility, 152 Anticytoskeletal antibodies, Bacterial motility, 152 immunogenic stimulus for, 57–58 Bacterial pathogens, 67, 68 Antigen-presenting cells (APCs), 51, 57 Barbed-end capping activity, 40, 41 Antimetastasis therapy, 146 Basement membrane (BM), 236 Antimicrofilament activity, 61 B-cell lymphoma 6 (BCL6), 244 Antinuclear antibody (ANA), 53 BDNF (brain-derived neurotrophic APC (antigen-presenting cells), 51, 57 factor), 118 Apical junctional complex (AJC), 154 β-actin, 27 Apicomplexan penetration of host cells, β-actin dysfunction, 283 309, 311 β-cytoplasmic actin, 56 Apicomplexan trophozoites, 310 β-galactosidase activity, 150 Aplysia neurons, 130 β-thalassemia, 211 Apoptosis, decreased, 140 β3-integrin expression, 146 Apoptosis-inducing drug, 46 β-tropomyosin, (TPM2), 22 APP (Amyloid precursor protein), Bilateral blindness, 111–112 128, 307 Blindness Arabidopsis thaliana, 294 myosin VIIa, mutations in, 76 ARDS (acute respiratory distress photoreceptor cell death, 76 syndrome), 193 BMP (bone morphogenic protein), 119 Arp2/3 and intracellular pathogens, Bone morphogenic protein (BMP), 119 299, 303 B-Raf gene, 107, 146 Arteriogenesis, 149 Brain-derived neurotrophic factor Atelosteogenesis, 286 (BDNF), 118 ATP depletion, 9, 134 ATP hydrolysis, 74, 131 C ATP-actin, 7 C. neoformans, 152 ATP-G-actin, 84 Cadherins (cell–cell adhesion), 235 Autoantibodies to F-actin. See F-actin Caenorhabditis elegans, 17, 93, 94, 109, autoantibodies 115, 135 Autoantigenicity of actin, 50 CAH (chronic active hepatitis), 53 Autoimmune hepatitis (AIH), 50 Calponin homology (CH), 69, 70, 70 autoimmune hepatitis, 52 Cancer, 77 epitopes of actin, 58 alterations in secretory pathways, 145 F-actin autoantibodies, 59 angiogenesis, 147 Index 339

cell proliferation and growth control, Chick cofilin, 87 142 Chromatin remodeling and cell transformation, 138 transcription, 9, 107, 108 decreased apoptosis, 140 Chronic active hepatitis (CAH), 53 gene expression and signaling, 138 Clonal selection theory, 51 metastasis, 146 Coatamer protein (COP), 105 morphological changes, 143 Cochlear fluid movements, 26 Cancer and apoptosis, gelsolin in, 194 Cofilin, 66 Cancer cell migration dephosphorylation, 143, 149 collective migration mode, 235 phosphorylation, 144, 146, 147 cell–substrate adhesion, 235 PIP2-binding site identification, 294 cell–cell adhesion, 235 rephosphorylation, 137 focal adhesion kinase (FAK), 235 Cofilin-1 null mice, 110 Cancer metastasis, Tβ4 (Thymosin β4) Cofilin-2, 110 in, 222 Cofilin-null embryos, 111 Capping proteins, 17, 66 Colony-stimulating factor (CSF), 240 Cardiac α-actin mutations. See Confocal scanning laser microscopy, 45 Cardiomyopathies for cardiac Congenital fiber-type disproportion α-actin mutations (CFTD), 16, 21 Cardiomyopathies for cardiac α-actin Congenital myopathies, 135 mutations Congenital skeletal myopathies cardiac and skeletal α-actin (ACTC1), 18 abundance, 321 ACTA1 myopathy mutations, familial , 320 molecular effects of, 23 familial hypertrophic cardiomyopathy, congenital fiber-type disproportion 318–320 (CFTD), 21 Cardiomyopathy (ACTC), 17. See also intranuclear actin rods, 20 Cardiomyopathies for cardiac α- nemaline rods, 19 actin mutations Core histone complexes, 9 Caspases, 141 Corneal disease, 111–112 CBD (corticobasal degeneration), 120 Corneal epithelial cell proliferation, Cdi (center divider), 113 112 Cell aging and cellular senescence, 150 Cortactin, 140 Cell motility, defects in Cortical actin penetration, 305 ABPs activity change, 68–69 Corticobasal degeneration (CBD), 120 neurological defects, 69 Costimulatory signaling pathway, 137 Cell polarity and polarized migration, Craniofacial dysmorphology, 120 102–104 Critical concentration, 5–6 Cell proliferation and growth control, CRP (cysteine-rich protein), 322 142 Cryptococcus neoformans, 152 Cell transformation (cancer), 138 Cyclin D1, 139 Cell turnover, 8 Cyclindependent kinase inhibitor, 143 Center divider (Cdi), 113 Cysteine-rich protein (CRP) family, 322 Central tolerance, 52 Cytokinesis, 101 CFTD (ongenital fiber-type Cytoplasmic actin buffer, 220 disproportion), 16, 21 Cytoplasmic actin genes, 16, 17 CH (calponin homology), 69, 70, 70 Cytoplasmic aggregates, 25 Chemotaxis, 279 Cytoplasmic rods (nemaline rods), 136 Chemotherapeutic drugs, 43 Cytoskeletal abnormality, 279 340 Index

Cytoskeletal , 27 EGFR (epidermal growth factor assembly, altered receptor), 238 regulation of, 293 Egress, viral. See Viral egress Elongation process, 7 D EMP, 121 DBP (vitamin D transport protein), 193. EMT (epithelial–mesemchymal See also Gc-globulin transition), 238, 239 DCM (dilated cardiomyopathy), 18 Ena/VASP proteins, 232, 233 Deafness, causes of. See Gamma actin Endocytosis, 302 (ACTG1) gene mutations and Endothelial development gene (Edg), deafness 149 Dementias, with neurological symptoms, Eosinophilic spherical structures, 132 120 Epidermal growth factor (EGF), 98 Dendrite arbor complexity, 116 Epidermal growth factor receptor Dendritic nucleation, 104 (EGFR), 238 Dendritic spine dysgenesis and synaptic Epidermal keratinocytes, 234 defects, 116 Epitopes of actin, 58 Dentate gyrus (DG), 129 EPSC (excitatory postsynaptic currents) Dephosphorylated cofilin-2, 135, 150 AMPAR, 119 ,88 NMDAR, 119 dFMRP (Drosophila homolog of ERK (extracellular receptor kinase), FMRP), 210 139 Diabetes (type 2), 293 Excitatory glutamatergic synapses, 116 Diacylglycerol (DAG), 290 Excitatory postsynaptic currents. See Dictyostelium discoideum, 20,109 EPSC Dihydrohalichondramide, structure of, Exocytosis, 305 40, 41, 42 Expression cloning technique, 284 Dilated cardiomyopathy (DCM), 18 Extracellular actin scavenging system Dominant tolerance, 52 (EASS), 192, 193 Doxorubicin-induced dilated Extracellular matrix. See ECM cardiomyopath, 325 Extracellular matrix, altered, 292 Drosophila, 113, 143, 210 Extracellular receptor kinase (ERK), Drosophila Lim kinase 1 (DLIMK1), 139 119 Ezrin dephosphorylation, 135 Drosophila melanogaster, 17, 101 Duchenne muscular dystrophy, 72 F Dystonia with dementia, 132 Fab fragments, 60, 62 , 72 F-actin assays, 25 E crosslinking protein, 27 E. coli helix, 27 , 28 enterohemorrhagic, 67 monomer, 6 enteropathogenic, 67, 68 polymerization, 22, 25 EASS (extracellular actin scavenging stability, 28 system), 192, 193 structure of, 4–5 ECM (extracellular matrix), 65, 70, 72, structures in nonmuscle cells, 86 73, 229, 235 F-actin autoantibodies Ectoplasmic specializations, 115 characteristics, 59 EGF (epidermal growth factor), 98 functional effects, 59–62 Index 341

F-actin (filaments), 1 Gametogenesis and reproductive FAF (familial amyloidosis of the problems, 113–115 Finnish type), 190 Gamma-actin, 27 FAK, (focal adhesion kinase), 238 Gamma actin (ACTG1) gene mutations Familial amyloidosis of Finnish type and deafness, 26–28 (FAF), 190 γ-cytoplasmic actin, 56 Familial cardiomyopathy, 17 γ-smooth muscle enteric actin, 56 Familial dilated cardiomyopathy (FDC), Gc-globulin, 193 320 Gel electrophoresis, 148 Familial hypertrophic cardiomyopathy Gelsolin, 286 (FHC), 318 activation of, 189 FDC (familial dilated cardiomyopathy), amyloidosis, 190–192 320 in cancer and apoptosis, 194–195 Fenestrae-forming center (FFC), 41 in extracellular actin scavenging Fenestrae-related disorder, 41 system, 192–194 FERM domain, 73 genes, 190 FFC (fenestrae-forming center), 41 structure, 188–189 FHC (Familial hypertrophic Gene expression and signaling, 9, 138 cardiomyopathy), 318 Gene mutation and deregulated gene Fiber-specific hypotrophy, 22 transcription Fibroblast cell motility, 194 ABPs, 242 Fibroblasts from OCRL Patients, 291 actin functional module activity in Filaments (F-actin), 1 prostate cancer, 253 Filamin, 285 altered transcription of ABP, 250 Filamin-related diseases, 72 deregulated expression in tumor cells, Filopodia formation, 305, 308 245 Fimbrin, 70 isoform specificities of ABP, 254 Finnish amyloidosis, 286 nuclear actin field, 256 Fluorescence microscopy, 298 parallel effector paths for protrusion Fluorescence resonance energy transfer formation, 252 methods, 107 GFAP (glial fibrilary acidic protein), Fluorescent membrane protein, 105 132 Fluorescent-labeled monoclonal GFP (green fluorescent protein), 131 antibodies, 291 Glanzmann’s thrombasthenia, 138 FMRP (fragile X mental retardation Glial fibrilary acidic protein (GFAP), protein), 124, 210 132 Focal adhesions (FA), 148, 231 Globular actin monomers (G-actin), 1 Focal contacts (FC), 231, 233 Glomerulosclerosis, 72, 73 Focal segmental glomerulosclerosis Glucose-regulated protein (GRP78), 140 mapping, 285 Glutaminergic synapses, 122 Forbidden clones, 52 glycosylphosphatidyinositol (GPI), 105 Fragile X mental retardation protein Golgi dynamics, 120 (FMRP), 124, 210 Golgi membrane dynamics, 83 Fragile X syndrome, 124, 125 Golgi tubule formation, 105, 106 Gomori trichrome staining, 19 G GPI (glycosylphosphatidyinositol), 105 G-actin (globular actin monomers), 1 G-protein-coupled receptor kinase- G-actin, structure of, 1-4 interacting protein 1 (GIT1), 123 G-actin-sequestering proteins, 84 Green fluorescent protein (GFP), 131 342 Index

H IIF (indirect immunofluorescence), 53, 57 Halichondramide, structure of, 40 ILK (integrin-linked kinase), 224, 238, 255 HBMEC (human brain microvascular Immune diseases endothelial cells), 152 platelet-dependent clotting disorders, HCM (hypertrophic cardiomyopathy), 137 17 T-cell activation, 136 Hearing loss, sensorineural, 76. See also Immune tolerance Gamma actin (ACTG1) gene central tolerance, 52 mutations and deafness forbidden clones, 52 Heart failure (role of actin and ABP). Immunity, 50 See Actin and ABP in heart failure Immunocytochemistry, 89 Hepatic endothelial fenestrae, 39 Immunodepletion of XAC, 153 Hepatic endothelium cells, 41–42 Immunogenic stimulus for Hepatocyte GF (HGF), 240 anticytoskeletal antibodies, 57–58 Hereditodegenerative dystonia, 132, 133 environmental antigen, 58 Herpesvirus, 306 epitope mimicry, 58 High-performance liquid spillage, 57 chromatography (HPLC), 282 Immunostaining of human brain, 128 Hippocampal dendritic spines, 117 Immunosuppressive drugs, 137 Hippocampal neurons, 128, 190 Inclusions (ADF/cofilin–actin enriched) Hirano bodies, 126, 127, 128 Alzheimer’s disease, 128–131 HIV infection, 303 dystonia with dementia, 132 Host cell actin cytoskeleton, 151, 298 ischemic kidney disease, 133–135 Host cell penetration, 308 rods and aggregates, 125–128 Human actin filament crosslinking stroke, 131–132 proteins, 71 Indirect immunofluorescence (IIF), 53 Human autoimmune antisera (Fab Inflammation, 149 fragments), 62 Inhibitor of apoptosis (IAP), 106 Human brain microvascular endothelial Innate immune system, 50 cells (HBMEC), 152 Integrins (cell–substrate adhesion), 235 Human cofilin, 87 Interleukin-1β-converting enzyme Human diploid fibroblast cells, 108 (ICE), 9 Intracellular pathogens and actin ACTB, 16 cytoskeleton ACTG1, 16 actin cytoskeleton, 299 cardiac (ACTC), 16 Arp2/3 machinery, 299 enteric (ACTG2), 16 host cell actin, 298 skeletal muscles (ACTA1), 16 protozoan intracellular parasites, smooth (ACTA2), 16 308 Human glomerular diseases, 209 viral effects (see Viruses) Human T-cell line, 194 viral egress, 305–308 Huntington’s chorea, 120 Intranuclear actin rods, 18, 20 Hydrophobic plug, 28 Intranuclear rod myopathy, 136 Hypertrophic cardiomyopathy (HCM), Intrinsic apoptosis pathway, 141 17, 75 Invasive bacteria, 151 Ischemic kidney disease, 133–135 I ICE (interleukin-1 β-converting J enzyme), 9 Jasplakinolide, 38, 44 Idiopathic dilated cardiomyopathy, 325 Jurkat cells, 194 Index 343

K M Kindler syndrome, 73 Macrophage chemotaxis, 148 Macrophages (MP), 236 L Mammalian genes L. monocytogenes, 308 ADF (destrin), 88 Lamella (LA), 231 cofilin-1 (n-cofilin), 88 Lamellipodium, 103, 104 cofilin-2 (m-cofilin), 88 Large tumor suppressor (LATS), 143 MAT, (mesemchymal–amoeboid Latrunculin A, 44 transition), 238 Lauryldimethylamine oxide (LDAO), Matrigel invasion assay, 144 294, 295 Matrix degrading enzymes, 147 Leufactin disease. See Neutrophil actin Matrix metalloproteinases (MMP), 238 dysfunction m-cofilin (muscle-type cofilin), 88, 90 LIM kinase, 115 Membrane lipids, 257 LIM proteins and heart failure Membrane ruffle protrusion, 103 altered expression of MLP, 324 Mental retardation, 122 CLP36, 325 Mesangial proliferative CRP2, 325 glomerulonephritis, 209 LMCD1, 324 Mesemchymal, 230 muscle LIM protein (MLP), 322 Mesenchymal to epithelial transition mutations in MLP, 323 (MET), 113 pathogenic mechanism, 324 MET (mesenchymal to epithelial Limb girdle disease, 28 transition), 113 LIMK (Lin-11, Isl-1, and Mec-3 Metalloproteinases, 145 kinase), 139, 140, 144 Metastasis, 146 LIMP (lysosome integral membrane Metastasis suppressor, 147 protein), 145 MHC (myosin heavy chain), 75, 243, Lipid-encapsulated drugs, 47 244 Lipopolysaccharide (LPS) endotoxins, network on cell 193 membranes, 279 Listeria monocytogenes, 151, 152, 153, -organizing center (MTOC), 154, 298, 299 301 Listeria motility, 154 Microvasculature permeability, 150 Liver and kidney microsomes (LKM), 53 Miller–Dieker Syndrome protein, 210 LKM (liver and kidney microsomes), 53 Misakinolide A, 40, 41 LNv (lateral neurons located Mitochondrial translocation, 141 ventrolaterally), 210 Mitochondrial-dependent apoptosis, 83, Long-distance virus transport, actin in, 85, 106 307 Mitogenic signal transduction pathways, Long-term depression (LTD), 119 43 Long-term potentiation (LTP), 119 MLC (myosin regulatory light chain), Lowe syndrome, 291 123 LPA (lysophosphatidic acid), 149 MLP (muscle LIM protein), 322 LPS (lipopolysaccharide), 193 altered expression, 324 LTD (long-term depression), 119 mutations, 323 LTP (long-term potentiation), 119 pathogenic mechanism, 324 Lupoid hepatitis, 53 MLV (mouse leukemia virus), 303 Lysophosphatidic acid (LPA), 149 MODS (multiple organ dysfunction Lysosome integral membrane protein syndrome), 193 (LIMP), 145 Monomeric G-actin, 55, 57 344 Index

Morphodynamics, 234 Nemaline phenotype, aspects of Mouse leukemia virus (MLV), 303 cytoplasmic aggregates, 25 mRNA delivery and translation, nuclear rods, 25 diseases of Nematode unc-60 gene, 109 fragile X syndrome, 124 NES (nuclear export signal), 21 overview, 123 Neural crest, 113 spinal muscular atrophy, 124 neuroblastoma (NB), 255 MTA (mesemchymal to amoeboid Neurodegenerative diseases, 120 movement), 239 Neurofibromatosis type 2 (NF2), 244, MTOC-TMA (microtubule organizing 249 center and transient microtubule Neurological dysfunction, 77 array), 115 Neuronal migration, 69 Multiphoton-based intravital imaging, Neutrophil actin dysfunction, 279, 281 237 with 47 kDa protein abnormalities, Multiple organ dysfunction syndrome 282 (MODS), 193 with 89 kDa protein abnormalities, Muscle LIM protein (MLP). See MLP 282 Muscle myosin mutation, 74, 75 Neutrophil cytoskeletal diseases, 280 Muscular dystrophy, 72, 135 Neutrophil immunodeficiency Musculoskeletal diseases syndrome. See Rac2 mutation muscular dystrophy, 135 NLS (nuclear localization sequence), nemaline myopathies (NM), 135 88 Myasthenia gravis, 60 NM-associated actin mutants, 136 Myelogenous leukemia (CML), 243 Nonmuscle cofilin, 115 MYH9-related disease, 77 Nonmuscle myosin, 286 Myofibril assembly, 110 mutations, cause of diseases Myofibrillar disorganization, 135 blindness, 76 Myofibroblasts (MF), 236 cancer, 77 Myosin heavy chain (MHC), 75, 243, hearing loss, 76 244 MYH9-related disease, 77 Myosin II regulatory light chain (MLC), neurological dysfunction, 77 123 Nonsarcomeric ABP mutations and Myosin XVIIIb, 77 heart failure DNase I, 327 N gelsolin, 328 NAD. See Neutrophil actin dysfunction N-terminal acetylation, 28 n-cofilin (nonmuscle-type cofilin), 88, Nuclear actin, 107, 108 89, 90 Nuclear and non-actin related activities, Nef, 303 256 Negative selection, 52 Nuclear export signal (NES), 21 Nemalin rods Nuclear import of actin, 107 cofilin, 18 Nuclear localization sequence (NLS), 88 nebulin (NEB), 18 Nuclear motility, 304 tropomyosin (TPM2 and TPM3), 18 Nuclear rods (AC and actin), 25, 126 T (TNNT1), 18 Nucleation process, 7 Z-disks, 20 Nucleotide hydrolysis, 7 zebra-bodies, 20 Nucleotide–cation complex, 3 Nemaline myopathy (NM), 24, 106, 135, Nucleus-cytoplasmic shuttling, 324 136. See also Nemalin rods nvadopodia, 147 Index 345

O regulation of cytoskeleton assembly, Oculocerebrorenal syndrome of Lowe 293 (OCRL), 291 PKC (protein kinase C), 209 Plasma gelsolin, 193 P Plasma membrane blebbing, 141 p21-activated kinases (PAKs), 96 Plasmodium falciparum, 154, 155, 309 PAF (platelet-activated factor), 284 Platelet-activated factor (PAF), 284 PAK, p21-activated kinase, 238 Platelet-dependent clotting disorders, PAK3 mutations, 122 137 Parallel effector paths for protrusion, PLC (phospholipase C), 238, 290 252 Plextrin homology (PH), 293 Parasite actin–myosin contractility, 308 PMA (phorbol-12-myristate-13-acetate), Parasite invasion, 309 284 Parkinson’s disease, 211 Podocytes, 292 Parkinsonism–dementia complex Podosomes, 140 (PDC), 126, 127 Polynueropathy, 190 Pathogenic bacteria and viruses Positive selection, 52 E. coli, 67, 68 Postsynaptic density (PSD), 118 Listeria,68 Profilin, 4, 101, 206 Rickettsia actin, 66, 68 actin, 201 Shigella, 66, 68 allergen, 207 Vaccinia, 66, 67, 68 Alzheimer’s disease, 210 PDC (Parkinsonism–dementia β-thalassemia, 211 complex), 126, 127 cancer. (see profiling, in Pedestals, 67, 68, 301, 302 cancer cells) Pericellular proteolysis, 239 fragile X syndrome, 210 Peripheral tolerance, 52 in cancer cells, 208 Phalloidin, 127 isoforms and functions, 205, 206 Phosphatidic acid (PA), 149P ligands, 200 Phosphatidylinositol (4,5) bisphosphate membrane Fraction, 204 (PI(4,5)P2. See PIP2 mesangial proliferative Phospholipase C (PLC), 290 glomerulonephritis, 209 PI-3K (phosphatidylinsitol-3-kinase), Miller–Dieker syndrome, 210 238 mutants, 202 PIP (phosphatidylinositol-phosphate p85α Subunit of PI3-kinase, binding) binding, 98 204 PIP2 and disease Parkinson’s disease, 211 altered cell signaling, 293 PIP-binding site, 202 altered extracellular matrix, 292 poly-L-proline sequences, 204 fibroblasts from OCRL patients, 291 polyphosphoinositides, 201 Lowe syndrome, 291 proline-rich motif (PRM) proteins, 204 type 2 diabetes, 293 Wiskott–Aldrich syndrome, 211 uncapping barbed ends of actin, 292 Protein kinase C (PKC), 209 PIP2 in actin Proteome analysis, 147, 148 location in cell, 290 Protozoan intracellular parasites metabolism, 290 actin and parasite invasion, 309 PIP2 in regulating ABPs parasite actin–myosin contractility, cofilin PIP2-binding site 308 identification, 294 PSD (postsynaptic density), 118 346 Index

R actin as reactant, 55 Rac2 mutation, 284 actin cables, 55 Receptor clustering, 302 muscle actins, 56 Recessive tolerance, 52 nonmuscle actins, 56 Regulatory protein mutation, 74, 75 reactivity by IIF, 54 Renal disorders, 72 Sodium dodecyl sulfate (SDS) Rho GTPases, 118, 123, 285 electrophoresis, 282 Rickettsia motility, 154 Space-filling model, 87 ROCK (Rho-associated kinase), 238, Spermatogenesis, 113, 114 239, 240 Sphingosine 1-phosphate (S1P), 149 Rods and aggregates, actin in, 125–128, Spilled antigen, 57 133 Spinal muscular atrophy, 124 Spine shrinkage, 119 S Spondylocarpotarsal syndrome (SCT), S1P (Sphingosine 1-phosphate), 149 286 Saccharomyces cerevisiae, 109 SRF (Serum response factor), 139, 142, SAGE (serial analysis of actin gene 322 expression), 242 Srv2/CAP family in yeast, 100 Salmonella invasion protein A (Sip A), SSH (phosphorylation-regulated 194, 151, 152 slingshot), 96, 97, 142, 144 Sarcomeric ABP mutations and heart Staphylococcus aureus, 282 failure Staurosporine, 106 α-actinin, 327 Stereocilia, 26-27, 28, 71, 76 α-tropomyosin, 327 Stroke, 131–132 , 326 Supravalvular aortic stenosis (SVAS), , 326 121 , 326 SVAS (supravalvular aortic stenosis), Sarcomeric isoforms, 85 121 Sarcomeric proteins, 18 Swinholide A, 40 Sarcomeric Z-disks, 19, 23 Synaptopodin 2 gene (SYNPO2) Sarcotubular myopathy, 29 coding, 250 Scaffolding protein, 76, 257 Systemic lupus erythematosus (SLE), 53 SDS (sodium dodecyl sulfate), 282 Secretory pathways, alterations in, T 145 T lymphocytes (T cells), 136 Senescent human diploid fibroblast TER (transmonolayer electrical cells, 150 resistance), 149, 150 Serial analysis of actin gene expression TESK (testicular kinase), 95, 96 (SAGE), 242 Testicular kinase (TESK), 95, 96 / kinase, 113 TGFβ-R, transforming growth factor Serum response factor (SRF), 139, receptor, 238 142, 322 Thrombocytopenia, 68, 69 Serum-induced apoptosis, 106 Thymosin β4 Sip A (Salmonella invasion protein A), amino acid sequence, 219 194 angiogenesis, 222 Skeletal muscle fibers, 21 binding activity with actin monomer, SLE (systemic lupus erythematosus), 220 53 in cancer metastasis, 222 Smooth muscle antibody (SMA), 53 cell migration, 223 Index 347

cell-to-cell signaling, 222, 223 V cellular functions, 223 Vaccinia virus, 304 discovery and properties, 218 Valine (D292V), 22 structural models, 221 Vascular actin, 56 in wound healing, 222 Vascular endothelial GF (VEGF), Thyrotrppin receptor (thyrotoxicosis), 240 60 Vasculogenesis, 148 Thyrotoxicosis, 60 Vasodilator-stimulated phosphoprotein Tissue expression pattern, 88 (VASP), 68, 139, 153, 258 TM. See Tropomyosins Vesicular stomatitis virus (VSV), 303 Tolerance and autoimmunity. See Viral egress Immune tolerance actin in long-distance virus transport, Toll-like receptors (TLR), 51 307 Transcription, 107 amyloid precursor protein, 307 Transendothelial transport, 39 anterograde transport, 306 Transforming growth factor β (TGFβ), filopodia, 308 142 herpesvirus, 306 Trans-Golgi network, 105, 191 Viral replication in nucleus, 304 Translational molecular psychiatry, Viral–host cell interactions, 300 123 Viruses Transmonolayer electrical resistance attachment, 302 (TER), 149, 150 effects on the actin cytoskeleton, Treadmilling of actin. See Actin, 300 polymerization of endocytosis, 302 Tropomyosins (TM), 83, 98-100, 255 nef, 303 Tropomyosin–troponin complex, 75 pedestals, 302 Troponin C, 326 receptor clustering, 302 Troponin I, 326 surfing, 302 Troponin T, 326 tails, 302 TSC (tuberous sclerosis complex), 122 vaccinia, 304 Tuberous sclerosis complex virus entry, 302 (TSC), 122 VSV (vesicular stomatitis virus), 303 Tumor cell invasion, matrix and host cells in W colony-stimulating factor WAS (Wiskott–Aldrich syndrome), 68, (CSF), 240 69, 211, 283 migration modes, 238 WBSCR1 (William–Beuren syndrome signaling pathways, 235 critical region 1), 121 Tumor cell metastasis, 146 Western blotting, 58 Tumor suppressor, 77 Williams syndrome (WS), 120, 122 Two-dimensional electrophoresis (2DE) WIP (WASp-interacting protein), 211, protein, 284 283 Tyrosine kinase inhibitors, 150 Wiskott–Aldrich syndrome (WAS), 68, Tβ4 (thymosin β4), 218 69, 211, 283 Wound healing assay, 145 U unc-60 gene, 109 X Upstream enzymes, 257 XAC (Xenopus ADF/cofilin), 101, 153 Usher syndrome type I, 76 XAC–GFP, 131, 134 348 Index

Xenopus ADF/cofilin (XAC), 101 Y Xenopus laevis, 101 Yeast cofilin, 87 X-linked nonsyndromic mental retardation, 122 Z XMR (X-linked mental retardation), Z-disc binding, 16 122 Zipcode-binding proteins, 124, 242 X-ray crystallography, 87 Zipper or trigger mechanism, 151