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. 2018 Aug;51:111-118.
doi: 10.1016/j.conb.2018.02.022. Epub 2018 Mar 22.

Shaping Neurodevelopment: Distinct Contributions of Cytoskeletal Proteins

Free PMC article

Shaping Neurodevelopment: Distinct Contributions of Cytoskeletal Proteins

Ngang Heok Tang et al. Curr Opin Neurobiol. .
Free PMC article


Development of a neuron critically depends on the organization of its cytoskeleton. Cytoskeletal components, such as tubulins and actins, have the remarkable ability to organize themselves into filaments and networks to support specialized and compartmentalized functions. Alterations in cytoskeletal proteins have long been associated with a variety of neurodevelopmental disorders. This review focuses on recent findings, primarily from forward genetic screens in Caenorhabditis elegans that illustrate how different tubulin protein isotypes can play distinct roles in neuronal development and function. Additionally, we discuss studies revealing new regulators of the actin cytoskeleton, and highlight recent technological advances in in vivo imaging and functional dissection of the neuronal cytoskeleton.

Conflict of interest statement

Conflict of interest statement

Nothing declared.


Figure 1
Figure 1. Cell biology and microtubule composition of cilia and mechanosensory neurons
(A) Schematic of cephalic male (CEM) ciliary neurons, BDU interneurons and mechanosensory ALM and PLM neurons in wild type C. elegans. (B) Top: Schematic of mechanosensory neurons in β-tubulin/mec-7 mutants. Bottom: Distinct mutations in tubulin affect microtubule (MT) function differently. Missense mutations predicted to interfere with tubulin polymerization (orange) resulted in reduced MT stability and defective PLM neurite outgrowth. Missense mutations affecting surface residues of the MTs (purple) may interfere with MT-associated protein or motor binding, leading to increased MT stability and ectopic ALM neurite outgrowth. The structure of the αβ-tubulin dimer (1jff.pdb) is shown on the right. Orange and purple stars mark the positions of representative mutations in the tubulin structure that affect neurite outgrowth. (C) Schematic of MT doublet in C. elegans CEM neurons. The MT doublet consists of an A-tubule with 13-pf MTs and a B-tubule with 10-pf MTs. (D) The tubulin glutamylase TTLL-11 and deglutamylase CCPP-1 regulate tubulin glutamylation in CEM neurons. Both hyperglutamylation in ccpp-1(0) mutants or hypoglutamylation in ttll-11(0) mutants result in reduced extracellular vesicle (EV) release.
Figure 2
Figure 2. Recent advances in microtubule imaging and study of cell type specific gene functions
(A) Expression of GFP::TBA-1/α-tubulin (MTs) and RFP::PTRN-1 (MT minus-end) proteins allows live imaging of MTs in vivo. MT length and spacing can be reconstructed following line scan of GFP::TBA-1 signals and visualized as a model to represent MT coverage and length [67]. (B) Schematic of ribosome imaging based on split GFP (RIBOS). A ribosomal protein is fused to the smaller part of split GFP (GFP11), whereas the larger part (GFP1-10) is expressed in specific cells (e.g. mechanosensory neurons). Upon coexpression of both transgenes, binding of GFP1-10 to GFP11 in the targeted cell allows visualization of ribosomes [29]. (C) Schematic of cell-specific degradation of GFP-tagged protein. A protein of interest is tagged with GFP, whereas the GFP nanobody-SOCS fusion gene (degron) is expressed in specific cells (e.g. mechanosensory neurons). Upon crossing of these strains, the degron binds to GFP-tagged proteins, promoting their ubiquitylation and subsequent protein degradation by the proteasome [71].

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