Cell Architecture: Putting the Building Blocks Together

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Cell architecture: putting the building blocks together

Editorial overview

Anna Akhmanova and Tim Stearns

Current Opinion in Cell Biology 2012, 25:xx–yy

0955-0674/$ – see front matter, # 2012 Elsevier

http://dx.doi.org/10.1016/j.ceb.2012.12.003

Anna Akhmanova

Cell Biology, Faculty of Science, Utrecht In considering cell architecture it is important to realize that for cells, as for

University, Padualaan 8, 3584 CH Utrecht,

buildings, the underpinning for the external shape is provided by a complex

The Netherlands

internal superstructure. And for cells, this cytoskeletal underpinning must

e-mail: [email protected]

be highly dynamic to effect the changes in morphology and organization

associated with division, growth and differentiation. Cytoskeletal elements

Anna Akhmanova is Professor of Cell Biology

at Utrecht University, the Netherlands, and a were some of the ﬁrst components of intracellular structure described by

member of EMBO. Her lab uses cell early microscopists in the late 19th century, but it was not until a century

biological approaches, in vitro reconstitutions later that the remarkable complexity of the cytoskeleton, in both compo-

and high-resolution microscopy to study

sition and behavior, has been revealed. Advances in genomics and proteo-

molecular mechanisms of microtubule

mics have provided us with near-comprehensive lists of the molecular

dynamics and vesicle trafficking and their

players associated with the various cytoskeletal systems. The challenge

contribution to mammalian development and

human disease. now is to understand how these components work together, and this is one of

the central themes of this issue of Current Opinion in Cell Biology.

Tim Stearns

Because of the highly interconnected nature of the cytoskeletal networks, it

Department of Biology, Stanford University,

Stanford, CA 94062, USA is often most useful to study individual components or systems in simpliﬁed

e-mail: [email protected] settings in vitro. Mullins and Hansen provide an overview of the recent in

vitro studies of actin network architecture and assembly. New methods of

Tim Stearns is Professor of Biology at

sample preparation and imaging provided insight into key features of actin

Stanford University and Professor of

polymerization and made it possible to perform reconstitutions where

Genetics at Stanford Medical School. His lab

cooperation between multiple actin regulators was recapitulated. By localiz-

studies the structure and function of the

ing actin nucleators to different substrates impressive progress has been

centrosome and cilium in animal cells and the

relationship of defects in these signaling made in reconstitution of protrusive actin networks and even cell spreading.

centers to human disease.

Microtubules have beneﬁted from recent in vitro approaches as well.

Gardner, Zanic and Howard review recent insights into the mechanisms

underlying the dynamic instability of microtubules. Studies in cells and in

vitro show that previously underappreciated phenomena such as microtu-

bule aging, the presence in the microtubule lattice of GTP-tubulin islands

and mechanical tension at microtubule ends can regulate the transitions

between microtubule growth and depolymerization. Dogterom and Surrey

discuss the progress in understanding how complex microtubule patterns are

generated and maintained. Although many types of microtubule arrange-

ments exist, they can be roughly categorized into three types: asters, anti-

parallel overlaps, and bundles. Complex reconstitution experiments with

puriﬁed microtubule motors, microtubule binding and bundling proteins

combined with modeling provide insights into how these patterns are

formed and positioned within the conﬁning geometry of cells.

One of the means by which cytoskeletal systems are regulated is

post-translational modiﬁcation of the major subunit proteins. Terman

and Kashina provide a comprehensive overview of all known covalent

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Please cite this article in press as: Akhmanova A, Stearns TCell architecture: putting the building blocks together, Curr Opin Cell Biol (2012), http://dx.doi.org/10.1016/j.ceb.2012.12.003

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2 Cell architecture

modiﬁcations of actin. The variety of known actin the nine-fold symmetry. In many cells the centriole

modiﬁcations is broad, ranging from conventional post- serves as a basal body for a cilium, which is involved in

translational modiﬁcations such as phosphorylation and important motility and sensory functions. Benmerah

acetylation to those much less studied, such as arginyla- focuses on a specialized membrane domain, the ciliary

tion and site-speciﬁc oxidation. These modiﬁcations con- pocket, that is at the base of cilium in many cells and is

tribute to the rich diversity of the regulatory mechanisms the site of membrane and protein trafﬁcking to and from

affecting actin dynamics and function. the cilium. This underappreciated structure might be

responsible for some of the specialized signaling roles

Actin is an essential player at the adherens junctions, that the cilium plays.

and recent studies are gradually revealing how actin

nucleating factors, motors and bundling proteins con- The cytoskeleton is closely associated with membrane

tribute to actin filament assembly and dynamics at the trafficking and dynamics. Angus and Griffiths discuss the

junctions. Brieher and Yap discuss the cross-talk be- complex set of events leading to the formation of

tween cadherin-based cell–cell junctions and the cytos- immunological synapse and polarized secretion by

keleton. Novel structural and signaling links between immune cells. Movement of the centrosome to the

microtubules and cadherin junctions are also being plasma membrane plays a key role in this process, and

discovered, indicating that microtubules are an recent studies have begun to reveal the cytoskeletal

important albeit a more variable regulator of these components and signalling molecules involved in centro-

structures. some relocalization and targeted delivery of cytolytic

granules. Like the immunological synapse, the cytoki-

Intermediate ﬁlaments were less well-studied during the netic furrow of animal cells is a site of polarized mem-

renaissance of interest in the cytoskeleton in the 60’s and brane trafﬁcking. Schiel and Prekeris review the events of

70’s. As described by Pan, Hobbs, and Coulombe, there is late cytokinesis, considering the role of endosomal mem-

much recent progress in understanding the role of kera- branes and how membrane dynamics are coordinated

tins, a prominent group of intermediate ﬁlaments. Ker- with the actin cytoskeleton, providing complementary

atins provide cells with structural support for shaping activities resulting in ﬁnal abscission.

tissues and individual organelles, including the nucleus,

but are also intimately involved in signaling, stress In another example of cytoskeletal involvement in polar-

response, apoptosis and cell motility, and in regulating izing cell components, Pratt and Mowry provide an over-

cell architecture in normal and pathological conditions. view of the recent advances in understanding mRNA

localization. This process depends on cis-acting signals

The relationship between the nucleus and cytoskeleton within localizing transcripts, and recent studies revealed

is further discussed by Tapley and Starr who focus on how their structures contribute to their functional proper-

the proteins that physically link the two. The LINC ties. High-resolution imaging experiments showed that

complex spans the nuclear envelope, establishing con- the intermediates of mRNA transport can be diverse:

nections between the nuclear lamina inside the nucleus while some transported mRNA are assembled into large

and a variety of cytoskeletal elements outside. These granules, others travel alone. Surprisingly, mRNA local-

connections are important in positioning the nucleus ization pathways can also intersect with endosomal sort-

within the cell, and the organization of organelles such ing, as the components of endocytic machinery

as the centrosome around the nucleus. Within the participate in mRNA anchoring.

nucleus there is another protein complex, cohesin, that

links sister chromatids. This chromatid cohesion is Understanding of cytoskeletal properties increasingly

essential for proper chromosome segregation in mitosis depends on mathematical modeling. Allard and Mogilner

and meiosis. Remeseiro and Losada review the mech- discuss a fascinating type of complex non-steady state

anisms by which cohesion is established in interphase cytoskeletal dynamics — self-organized actin travelling

and released in mitosis, and additional roles that cohe- waves. Waves of protrusion, retraction and actin density

sin plays in DNA damage repair and interphase chro- can be observed in a broad variety of cells and might help

matin structure. them to avoid obstacles or squeeze through the extra-

cellular matrix. The diverse types of waves result from

Many elements of the cytoskeleton are characterized by activation and inhibition feedbacks in actin dynamics,

highly ordered arrangement of protein subunits. The and their mechanisms can only be understood through a

centrioles at the core of the centrosome are an extreme tight combination of experiments and theory.

example, with a highly-conserved nine-fold symmetric

structure and deﬁned length. The centrioles are dupli- One of the keys to understanding complex cellular pro-

cated once per cell cycle, and Avidor-Reiss and Gopa- cesses is to be able to challenge cells with substrates that

lakrishnan discuss the proteins and processes involved in probe biology which is not accessible to the long-time

building the centriole, including the molecular basis of standards, the coverslip and Petri dish. Lautenschla¨ger

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Please cite this article in press as: Akhmanova A, Stearns TCell architecture: putting the building blocks together, Curr Opin Cell Biol (2012), http://dx.doi.org/10.1016/j.ceb.2012.12.003

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Editorial overview Akhmanova 3

and Piel describe advances in microfabricated tools for As an example of the beneﬁts of broadening our view of

assaying cells, ranging from the simple, such as linear model organisms, Zhang and Oliferenko highlight recent

surfaces for cell migration, to the complex, such as sub- advances in understanding cell cycle-dependent nuclear

strates to mimic human tissues. envelope dynamics in related organisms with closed

mitosis. Closed nuclear division requires nuclear mem-

For many years it was assumed that prokaryotic cells brane expansion, which depends on cell cycle regulated

lacked the complex cytoskeletal systems of eukaryotic changes in lipid metabolism and membrane remodeling.

cells. Pilhofer and Jensen dispel that notion, describing Interestingly, nuclear division displays surprising evol-

the many forms of bacterial cytoskeletal filaments and the utionary flexibility: while the fission yeast Schizosacchar-

roles that they play in cell division and morphology. omyces pombe undergoes a classical closed nuclear division,

Remarkably, some of the bacterial cytoskeletal elements another ﬁssion yeast, Schizosaccharomyces japonicus,

are derived from proteins that are relatives of the major initiates closed mitosis but the nucleus ruptures in late

eukaryotic subunit proteins actin and tubulin, demon- anaphase. This suggests that relatively modest adjust-

strating that cytoskeletal polymers were one of the fea- ments in cell physiology can lead to signiﬁcant changes in

tures of the earliest forms of life. Dawson and Paredez cell division mechanisms.

describe the fascinating complexity of cytoskeletal ‘land-

scapes’ in protozoa. Excavate protists, which are regarded In sum, the set of reviews in this issue provides insight

as one the deepest branching groups of eukaryotes, pos- into a broad range of problems and approaches at the

sess unique and spectacular arrangements of microtu- forefront of research on cell architecture and the cytos-

bules and actin ﬁlaments, but can lack canonical keleton. The topics demonstrate that as the parts list of

regulatory factors, such as, for example, myosin and cellular components becomes established, the focus of

regulators of the Arp2/3 complex. On the other hand, research is shifting to studies of the relationships and

these organisms contain many novel genes and thus regulation, which govern the dynamic processes that are

represent a rich source for discovering novel cytoskeletal essential for normal function and that are defective in

mechanisms. many disease states.

www.sciencedirect.com Current Opinion in Cell Biology 2012, 25:1–3

Please cite this article in press as: Akhmanova A, Stearns TCell architecture: putting the building blocks together, Curr Opin Cell Biol (2012), http://dx.doi.org/10.1016/j.ceb.2012.12.003