Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia

Bowen, Jonathan R.; Hwang, Daniel; X, Bai; Roy, Dheeraj S.; Spiliotis, Elias T.

doi:10.1083/jcb.201102076

Cited by 129 publications

(149 citation statements)

References 54 publications

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“…This might indicate the presence of unknown structures in polarized epithelial cells that anchor MTCL1 to maintain its sublateral localization. Recently, filamentous GTPases (septins) were shown to guide the directionality of MT plus-end movement and support MT remodeling in polarizing epithelial cells (Bowen et al, 2011). It will be interesting to examine whether the septin scaffold provides the structural anchoring sites for MTCL1 at the sublateral cortex of polarized epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The interactions between APC, LL5, KIF17 and MT-plus-end-tracking proteins (+TIPs) were further demonstrated to be involved in membrane anchoring of the plus ends of these MTs and their stabilization (Hotta et al, 2010;Jaulin and Kreitzer, 2010;Mogensen et al, 2002). A recent study revealed that septin filaments navigate the growth and positioning of MTs along the apicobasal axis (Bowen et al, 2011). However, the mechanisms that promote MT assembly into higher-order structures (bundles) have not been clarified.…”

Section: Introductionmentioning

confidence: 99%

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A novel PAR-1-binding protein, MTCL1, plays critical roles in organizing microtubules in polarizing epithelial cells

Sato

Akitsu

Amano

et al. 2013

Journal of Cell Science

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SummaryThe establishment of epithelial polarity is tightly linked to the dramatic reorganization of microtubules (MTs) from a radial array to a vertical alignment of non-centrosomal MT bundles along the lateral membrane, and a meshwork under the apical and basal membranes. However, little is known about the underlying molecular mechanism of this polarity-dependent MT remodeling. The evolutionarily conserved cell polarity-regulating kinase PAR-1 (known as MARK in mammals), whose activity is essential for maintaining the dynamic state of MTs, has indispensable roles in promoting this process. Here, we identify a novel PAR-1-binding protein, which we call microtubule crosslinking factor 1 (MTCL1), that crosslinks MTs through its N-terminal MT-binding region and subsequent coiledcoil motifs. MTCL1 colocalized with the apicobasal MT bundles in epithelial cells, and its knockdown impaired the development of these MT bundles and the epithelial-cell-specific columnar shape. Rescue experiments revealed that the N-terminal MT-binding region was indispensable for restoring these defects of the knockdown cells. MT regrowth assays indicated that MTCL1 was not required for the initial radial growth of MTs from the apical centrosome but was essential for the accumulation of non-centrosomal MTs to the sublateral regions. Interestingly, MTCL1 recruited a subpopulation of PAR-1b (known as MARK2 in mammals) to the apicobasal MT bundles, and its interaction with PAR-1b was required for MTCL1-dependent development of the apicobasal MT bundles. These results suggest that MTCL1 mediates the epithelial-cell-specific reorganization of non-centrosomal MTs through its MT-crosslinking activity, and cooperates with PAR-1b to maintain the correct temporal balance between dynamic and stable MTs within the apicobasal MT bundles.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel PAR-1-binding protein, MTCL1, plays critical roles in organizing microtubules in polarizing epithelial cells

Sato

Akitsu

Amano

et al. 2013

Journal of Cell Science

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“…These protein interaction networks, which are based around CLASP2, also appear to be related to the functional coupling of the Golgi and the centrosome during processes such as their coupled relocalization to the front of migrating epithelial cells (Hurtado et al, 2011). The TGN-nucleated microtubule array is aligned with septin filaments (Spiliotis et al, 2008) and ultimately forms a post-translationally modified set of microtubules that is generated by septins, which can act directly on microtubule dynamics (Bowen et al, 2011). At least in some cells, this network has a role in the targeted delivery of cargo to the plasma membrane (Schmoranzer et al, 2003;Dunn et al, 2008;Yadav et al, 2009).…”

Section: Nucleation Of Microtubules By Membranes and Implications Formentioning

confidence: 99%

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

Stephens

2012

Journal of Cell Science

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SummaryThe microtubule network dictates much of the spatial patterning of the cytoplasm, and the coupling of microtubules to membranes controls the structure and positioning of organelles and directs membrane trafficking between them. The connection between membranes and the microtubule cytoskeleton, and the way in which organelles are shaped and moved by interactions with the cytoskeleton, have been studied intensively in recent years. In particular, recent work has expanded our thinking of this topic to include the mechanisms by which membranes are shaped and how cargo is selected for trafficking as a result of coupling to the cytoskeleton. In this Commentary, I will discuss the molecular basis for membrane-motor coupling and the physiological outcomes of this coupling, including the way in which microtubule-based motors affect membrane structure, cargo sorting and vectorial trafficking between organelles. Whereas many core concepts of these processes are now well understood, key questions remain about how the coupling of motors to membranes is established and controlled, about the regulation of cargo and/or motor loading and about the control of directionality.

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“…Septins are filamentous guanine triphosphates (GTPases) that can bind to microtubules [reviewed by Kinoshita, 2006;Weirich et al, 2008;Spiliotis, 2010]. In epithelial cells undergoing polarization, septin 2 associated with bundled microtubules guides microtubule growth dynamics and microtubule-microtubule interactions toward the establishment of the apical microtubule meshwork [Bowen et al, 2011]. The septin tracks also facilitate post-Golgi vesicle transport by antagonizing MAP4, which has an inhibitory role in vesicle transport.…”

Section: Epithelial Cell Polarizationmentioning

confidence: 99%

Shaping microtubules into diverse patterns: Molecular connections for setting up both ends

Mimori-Kiyosue¹

2011

Cytoskeleton

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Microtubules serve as rails for intracellular trafficking and their appropriate organization is critical for the generation of cell polarity, which is a foundation of cell differentiation, tissue morphogenesis, ontogenesis and the maintenance of homeostasis. The microtubule array is not just a static railway network; it undergoes repeated collapse and reassembly in diverse patterns during cell morphogenesis. In the last decade much progress has been made toward understanding the molecular mechanisms governing complex microtubule patterning. This review first revisits the basic principle of microtubule dynamics, and then provides an overview of how microtubules are arranged in highly shaped and functional patterns in cells changing their morphology by factors controlling the fate of microtubule ends. V C 2011 Wiley Periodicals, Inc.

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Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia

Abstract: Filamentous and microtubule-associated septin GTPases guide the reorganization of the microtubule network during epithelial cell polarization.

Cited by 129 publications

References 54 publications

A novel PAR-1-binding protein, MTCL1, plays critical roles in organizing microtubules in polarizing epithelial cells

A novel PAR-1-binding protein, MTCL1, plays critical roles in organizing microtubules in polarizing epithelial cells

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

Shaping microtubules into diverse patterns: Molecular connections for setting up both ends

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