Slit Proteins: Molecular Guidance Cues for Cells Ranging from Neurons to Leukocytes Kit Wong, Hwan Tae Park*, Jane Y Wu* and Yi Rao†
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Neurexin Ilia: Extensive Alternative Splicing Generates Membrane-Bound and Soluble Forms Yuri A
Proc. Natl. Acad. Sci. USA Vol. 90, pp. 6410-6414, July 1993 Biochemistry Neurexin IlIa: Extensive alternative splicing generates membrane-bound and soluble forms YURi A. USHKARYOV AND THOMAS C. SUDHOF* Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical School, Dallas, TX 75235 Communicated by Michael S. Brown, March 26, 1993 ABSTRACT The structure ofneurexin lIa was elucidated and 13-neurexins have identical C termini including the from overlapping cDNA clones. Neurexin lIa is highly ho- 0-linked sugar region, transmembrane region, and cytoplas- mologous to neurexins la and Ha and shares with them a mic domain (2). distinctive domain structure that resembles a cell surface Structures of the neurexins are suggestive of cell surface receptor. cDNA cloning and PCR experiments revealed alter- receptors. Indeed, the neurexins were originally found be- native splicing at four positions in the mRNA for neurexin HIa. cause of the identity of the sequence of neurexin Ia and Alternative splicing was previously observed at the same po- sequences from the high molecular weight subunit of the sitions in either neurexin Ia or neurexin Ila or both, suggesting receptor for a presynaptic neurotoxin, a-latrotoxin (7). Im- that the three neurexins are subject to extensive alternative munocytochemistry ofrat brain frozen sections revealed that splicing. This results in hundreds of different neurexins with neurexin I is highly enriched in synapses in agreement with variations in small sequences at similar positions in the pro- the localization of a-latrotoxin (2). These findings suggest teins. The most extensive alternative splicing of neurexin Ma that at least neurexins Ia and I13 are synaptic proteins that, was detected at its C-terminal site, which exhibits a minimum based on their structure and homologies, may represent a of 12 variants. -
Understanding Axon Guidance: Are We Nearly There Yet?
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2018 Understanding axon guidance: are we nearly there yet? Stoeckli, Esther T Abstract: During nervous system development, neurons extend axons to reach their targets and form functional circuits. The faulty assembly or disintegration of such circuits results in disorders of the nervous system. Thus, understanding the molecular mechanisms that guide axons and lead to neural circuit formation is of interest not only to developmental neuroscientists but also for a better comprehension of neural disorders. Recent studies have demonstrated how crosstalk between different families of guidance receptors can regulate axonal navigation at choice points, and how changes in growth cone behaviour at intermediate targets require changes in the surface expression of receptors. These changes can be achieved by a variety of mechanisms, including transcription, translation, protein-protein interactions, and the specific trafficking of proteins and mRNAs. Here, I review these axon guidance mechanisms, highlighting the most recent advances in the field that challenge the textbook model of axon guidance. DOI: https://doi.org/10.1242/dev.151415 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-166034 Journal Article Published Version Originally published at: Stoeckli, Esther T (2018). Understanding axon guidance: are we nearly there yet? Development, 145(10):dev151415. DOI: https://doi.org/10.1242/dev.151415 © 2018. Published by The Company of Biologists Ltd | Development (2018) 145, dev151415. doi:10.1242/dev.151415 REVIEW Understanding axon guidance: are we nearly there yet? Esther T. -
PRODUCT SPECIFICATION Product Datasheet
Product Datasheet QPrEST PRODUCT SPECIFICATION Product Name QPrEST SLIT3 Mass Spectrometry Protein Standard Product Number QPrEST21571 Protein Name Slit homolog 3 protein Uniprot ID O75094 Gene SLIT3 Product Description Stable isotope-labeled standard for absolute protein quantification of Slit homolog 3 protein. Lys (13C and 15N) and Arg (13C and 15N) metabolically labeled recombinant human protein fragment. Application Absolute protein quantification using mass spectrometry Sequence (excluding CDNKNDSANACSAFKCHHGQCHISDQGEPYCLCQPGFSGEHCQQENPCLG fusion tag) QVVREVIRRQKGYASCATASKVPIMECRG Theoretical MW 26448 Da including N-terminal His6ABP fusion tag Fusion Tag A purification and quantification tag (QTag) consisting of a hexahistidine sequence followed by an Albumin Binding Protein (ABP) domain derived from Streptococcal Protein G. Expression Host Escherichia coli LysA ArgA BL21(DE3) Purification IMAC purification Purity >90% as determined by Bioanalyzer Protein 230 Purity Assay Isotopic Incorporation >99% Concentration >5 μM after reconstitution in 100 μl H20 Concentration Concentration determined by LC-MS/MS using a highly pure amino acid analyzed internal Determination reference (QTag), CV ≤10%. Amount >0.5 nmol per vial, two vials supplied. Formulation Lyophilized in 100 mM Tris-HCl 5% Trehalose, pH 8.0 Instructions for Spin vial before opening. Add 100 μL ultrapure H2O to the vial. Vortex thoroughly and spin Reconstitution down. For further dilution, see Application Protocol. Shipping Shipped at ambient temperature Storage Lyophilized product shall be stored at -20°C. See COA for expiry date. Reconstituted product can be stored at -20°C for up to 4 weeks. Avoid repeated freeze-thaw cycles. Notes For research use only Product of Sweden. For research use only. Not intended for pharmaceutical development, diagnostic, therapeutic or any in vivo use. -
From Bipotent Neuromesodermal Progenitors to Neural-Mesodermal Interactions During Embryonic Development
International Journal of Molecular Sciences Review From Bipotent Neuromesodermal Progenitors to Neural-Mesodermal Interactions during Embryonic Development Nitza Kahane and Chaya Kalcheim * Department of Medical Neurobiology, Institute of Medical Research Israel-Canada (IMRIC) and the Edmond and Lily Safra Center for Brain Sciences (ELSC), Hebrew University of Jerusalem-Hadassah Medical School, P.O. Box 12272, Jerusalem 9112102, Israel; [email protected] * Correspondence: [email protected] Abstract: To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes. Following early gastrulation, while the vertebrate body elongates, a pop- ulation of bipotent neuromesodermal progenitors resident in the posterior region of the embryo generate both neural and mesodermal lineages. At later stages, the somitic mesoderm regulates aspects of neural patterning and differentiation of both central and peripheral neural progenitors. Reciprocally, neural precursors influence the paraxial mesoderm to regulate somite-derived myogen- esis and additional processes by distinct mechanisms. Central to this crosstalk is the activity of the axial notochord, which, via sonic hedgehog signaling, plays pivotal roles in neural, skeletal muscle and cartilage ontogeny. Here, we discuss the cellular and molecular basis underlying this complex Citation: Kahane, N.; Kalcheim, C. developmental plan, with a focus on the logic of sonic hedgehog activities in the coordination of the From Bipotent Neuromesodermal Progenitors to Neural-Mesodermal neural-mesodermal axis. -
The Neuronal Repellent SLIT2 Is a Target for Repression by EZH2 in Prostate Cancer
Oncogene (2010) 29, 5370–5380 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc ORIGINAL ARTICLE The neuronal repellent SLIT2 is a target for repression by EZH2 in prostate cancer JYu1,2,3,4, Q Cao2,3,JYu2,LWu1, A Dallol5,JLi2, G Chen2, C Grasso2,3, X Cao2,3, RJ Lonigro2,4, S Varambally2,3, R Mehra2,3, N Palanisamy2,3,JYWu1,8, F Latif5 and AM Chinnaiyan2,3,4,6,7 1Division of Hematology/Oncology, Department of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA; 2Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; 3Department of Pathology, University of Michigan, Ann Arbor, MI, USA; 4Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; 5Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Edgbaston, UK; 6Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA; 7Department of Urology, University of Michigan, Ann Arbor, MI, USA and 8Department of Neurology, Lurie Comprehensive Cancer Center, Center for Genetic Medicine, Northwestern University, Chicago, IL, USA The neuronal repellent SLIT2 is repressed in a number of also includes SLIT1 and SLIT3. The SLIT proteins are cancer types primarily through promoter hypermethyla- evolutionary conserved and contain an N-terminal signal tion. SLIT2, however, has not been studied in prostate peptide, four leucine-rich tandem repeats, seven or nine cancer. Through genome-wide location analysis we epidermal growth factor repeats, a laminin G domain and a identified SLIT2 as a target of polycomb group (PcG) C-terminal cysteine knot (Rothberg et al., 1988). -
Slit1 and Slit2 Cooperate to Prevent Premature Midline Crossing of Retinal Axons in the Mouse Visual System
Neuron, Vol. 33, 219–232, January 17, 2002, Copyright 2002 by Cell Press Slit1 and Slit2 Cooperate to Prevent Premature Midline Crossing of Retinal Axons in the Mouse Visual System Andrew S. Plump,1,2,6 Lynda Erskine,3,6,7 midbrain. Some axons do not cross, projecting to the Christelle Sabatier,1 Katja Brose,1 same targets but ipsilaterally. As with many other brain Charles J. Epstein,2 Corey S. Goodman,4 commissures, formation of the optic chiasm occurs at Carol A. Mason,3 and Marc Tessier-Lavigne1,5,8 an invariant position along the antero-posterior axis of 1 Departments of Anatomy and the developing forebrain. Mechanisms must therefore of Biochemistry and Biophysics exist not only to direct divergence at the midline but also Howard Hughes Medical Institute to prevent retinal axons from crossing at inappropriate 2 Division of Medical Genetics locations. University of California, San Francisco While significant progress in recent years has led to San Francisco, California 94143 a greater understanding of the factors that help establish 3 Departments of Pathology, Anatomy, a topographic map within the retina and its targets and Cell Biology (O’Leary et al., 1999), less progress has been made in Center for Neurobiology and Behavior identifying the rudimentary axon guidance cues that es- Columbia University College of Physicians tablish the basic trajectories within the vertebrate visual and Surgeons system, particularly those that function at the midline New York, New York 10032 to regulate the positioning and decussation of retinal 4 Department of Molecular and Cell Biology axons. In mammals, chondroitin sulfate proteoglycans Howard Hughes Medical Institute (CSPGs), L1, netrin-1, and specific EphB ligands are University of California, Berkeley important for guidance within the retina (Birgbauer et Berkeley, California 94720 al., 2000; Brittis et al., 1992, 1995; Deiner et al., 1997; Snow et al., 1991). -
Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?
biomolecules Review Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison? Rosa Manzoli 1,2,†, Lorenzo Badenetti 1,3,4,†, Michela Rubin 1 and Enrico Moro 1,* 1 Department of Molecular Medicine, University of Padova, 35121 Padova, Italy; [email protected] (R.M.); [email protected] (L.B.); [email protected] (M.R.) 2 Department of Biology, University of Padova, 35121 Padova, Italy 3 Department of Women’s and Children’s Health, University of Padova, 35121 Padova, Italy 4 Pediatric Research Institute “Città della Speranza”, 35127 Padova, Italy * Correspondence: [email protected]; Tel.: +39-04-98276341 † These authors contributed equally to this paper. Abstract: Axonal trajectories and neural circuit activities strongly rely on a complex system of molec- ular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely un- derstood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases. Citation: Manzoli, R.; Badenetti, L.; Keywords: axon guidance; lysosomal storage disorders; neuronal circuit Rubin, M.; Moro, E. Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison? Biomolecules 2021, 11, 191. -
Discovery of a Functional Protein Complex of Netrin-4, Laminin 1 Chain
Discovery of a functional protein complex of netrin-4, laminin ␥1 chain, and integrin ␣61 in mouse neural stem cells Fernanda I. Staquicinia, Emmanuel Dias-Netoa, Jianxue Lib, Evan Y. Snyderc,d,e, Richard L. Sidmanb,1, Renata Pasqualinia,1, and Wadih Arapa,1 aDavid H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; bHarvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215; cStem Cell and Regeneration Program, Center for Neuroscience and Aging Research, Burnham Institute for Medical Research, La Jolla, CA 92037; dDepartment of Pediatrics, University of California, School of Medicine, La Jolla, CA 92093; and eSan Diego Consortium for Regenerative Medicine, La Jolla, CA 92037 Contributed by Richard L. Sidman, December 29, 2008 (sent for review October 13, 2008) Molecular and cellular interactions coordinating the origin and fate timeric complex functions as an integrated supramolecular of neural stem cells (NSCs) in the adult brain are far from being switch that regulates NSC fate. understood. We present a protein complex that controls prolifer- ation and migration of adult NSCs destined for the mouse olfactory Results and Discussion bulb (OB). Combinatorial selection based on phage display tech- Isolation of Peptides Binding to NSCs and Receptor Identification. We nology revealed a previously unrecognized complex between the profiled (16–18) the surface of a representative prototypical soluble protein netrin-4 and laminin ␥1 subunit that in turn clone of murine NSCs (C17.2) that can self-renew, differentiate activates an ␣61 integrin-mediated signaling pathway in NSCs. into all neural lineages, and populate developing or degenerating Differentiation of NSCs is accompanied by a decrease in netrin-4 regions of the central nervous system (19, 20). -
Supplementary Table 1: Adhesion Genes Data Set
Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like, -
Dynamic Landscape of Chromatin Accessibility and Transcriptomic
www.nature.com/scientificreports OPEN Dynamic landscape of chromatin accessibility and transcriptomic changes during diferentiation of human embryonic stem cells into dopaminergic neurons César Meléndez‑Ramírez1,2,6, Raquel Cuevas‑Diaz Duran3,6*, Tonatiuh Barrios‑García3, Mayela Giacoman‑Lozano3, Adolfo López‑Ornelas1,2,4, Jessica Herrera‑Gamboa3, Enrique Estudillo2, Ernesto Soto‑Reyes5, Iván Velasco1,2* & Víctor Treviño3* Chromatin architecture infuences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic diferentiation have identifed coding genes, but the relationship with non‑coding genes or chromatin accessibility remains elusive. Using RNA‑Seq and ATAC‑Seq we profled diferentially expressed transcripts and open chromatin regions during early dopaminergic neuron diferentiation. Hierarchical clustering of diferentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non‑coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon diferentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specifc functional pathways and gene‑sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic diferentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC‑binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co‑localization of CTCF with Polycomb‑repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and diferentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity. -
Mouse Slit1 Conditional Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Slit1 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Slit1 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Slit1 gene (NCBI Reference Sequence: NM_015748 ; Ensembl: ENSMUSG00000025020 ) is located on Mouse chromosome 19. 37 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 37 (Transcript: ENSMUST00000025993). Exon 6~8 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Slit1 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-332I24 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a reporter allele exhibit normal interneuron numbers and morphology. Exon 6 starts from about 10.58% of the coding region. The knockout of Exon 6~8 will result in frameshift of the gene. The size of intron 5 for 5'-loxP site insertion: 992 bp, and the size of intron 8 for 3'-loxP site insertion: 1117 bp. The size of effective cKO region: ~1526 bp. The cKO region does not have any other known gene. Page 1 of 7 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 5 6 7 8 9 10 11 37 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Slit1 Homology arm cKO region loxP site Page 2 of 7 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. -
SLIT3 (NM 003062) Human Untagged Clone – SC118202 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for SC118202 SLIT3 (NM_003062) Human Untagged Clone Product data: Product Type: Expression Plasmids Product Name: SLIT3 (NM_003062) Human Untagged Clone Tag: Tag Free Symbol: SLIT3 Synonyms: MEGF5; SLIL2; Slit-3; SLIT1; slit2 Vector: pCMV6-XL4 E. coli Selection: Ampicillin (100 ug/mL) Cell Selection: None Fully Sequenced ORF: >OriGene ORF sequence for NM_003062 edited ATGGCCCCCGGGTGGGCAGGGGTCGGCGCCGCCGTGCGCGCCCGCCTGGCGCTGGCCTTG GCGCTGGCGAGCGTCCTGAGTGGGCCTCCAGCCGTCGCCTGCCCCACCAAGTGTACCTGC TCCGCTGCCAGCGTGGACTGCCACGGGCTGGGCCTCCGCGCGGTTCCTCGGGGCATCCCC CGCAACGCTGAGCGCCTTGACCTGGACAGAAATAATATCACCAGGATCACCAAGATGGAC TTCGCTGGGCTCAAGAACCTCCGAGTCTTGCATCTGGAAGACAACCAGGTCAGCGTCATC GAGAGAGGCGCCTTCCAGGACCTGAAGCAGCTAGAGCGACTGCGCCTGAACAAGAATAAG CTGCAAGTCCTTCCAGAATTGCTTTTCCAGAGCACGCCGAAGCTCACCAGACTAGATTTG AGTGAAAACCAGATCCAGGGGATCCCGAGGAAGGCGTTCCGCGGCATCACCGATGTGAAG AACCTGCAACTGGACAACAACCACATCAGCTGCATTGAAGATGGAGCCTTCCGAGCGCTG CGCGATTTGGAGATCCTTACCCTCAACAACAACAACATCAGTCGCATCCTGGTCACCAGC TTCAACCACATGCCGAAGATCCGAACTCTGCGCCTCCACTCCAACCACCTGTACTGCGAC TGCCACCTGGCCTGGCTCTCGGATTGGCTGCGACAGCGACGGACAGTTGGCCAGTTCACA CTCTGCATGGCTCCTGTGCATTTGAGGGGCTTCAACGTGGCGGATGTGCAGAAGAAGGAG TACGTGTGCCCAGCCCCCCACTCGGAGCCCCCATCCTGCAATGCCAACTCCATCTCCTGC CCTTCGCCCTGCACGTGCAGCAATAACATCGTGGACTGTCGAGGAAAGGGCTTGATGGAG ATTCCTGCCAACTTGCCGGAGGGCATCGTCGAAATACGCCTAGAACAGAACTCCATCAAA GCCATCCCTGCAGGAGCCTTCACCCAGTACAAGAAACTGAAGCGAATAGACATCAGCAAG