| Structural highlights
Function
[DPYL2_HUMAN] Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity). Plays a role in neuron projection morphogenesis.[1] [2]
Publication Abstract from PubMed
Microtubule associated protein Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity in developing neurons through interactions with tubulins or microtubules. However, how CRMP2 promotes axonal formation by affecting microtubule behavior remains unknown. This study aimed to obtain the structural basis for CRMP2-tubulin/microtubule interaction in the course of axonogenesis. The X-ray structural studies indicated that the main interface to the soluble tubulin-dimer is the last helix H19 of CRMP2 that is distinct from the known C-terminal tail-mediated interaction with assembled microtubules. In vitro structural and functional studies also suggested that the H19-mediated interaction promoted the rapid formation of GTP-state microtubules directly, which is an important feature of the axon. Consistently, the H19 mutants disturbed axon elongation in chick neurons, and failed to authorize the structural features for axonal microtubules in Caenorhabditis elegans. Thus, CRMP2 induces effective axonal microtubule formation through H19-mediated interactions with a soluble tubulin-dimer allowing axonogenesis to proceed.
Structural basis for CRMP2-induced axonal microtubule formation.,Niwa S, Nakamura F, Tomabechi Y, Aoki M, Shigematsu H, Matsumoto T, Yamagata A, Fukai S, Hirokawa N, Goshima Y, Shirouzu M, Nitta R Sci Rep. 2017 Sep 6;7(1):10681. doi: 10.1038/s41598-017-11031-4. PMID:28878401[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Inagaki N, Chihara K, Arimura N, Menager C, Kawano Y, Matsuo N, Nishimura T, Amano M, Kaibuchi K. CRMP-2 induces axons in cultured hippocampal neurons. Nat Neurosci. 2001 Aug;4(8):781-2. PMID:11477421 doi:http://dx.doi.org/10.1038/90476
- ↑ Cole AR, Knebel A, Morrice NA, Robertson LA, Irving AJ, Connolly CN, Sutherland C. GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons. J Biol Chem. 2004 Nov 26;279(48):50176-80. Epub 2004 Oct 5. PMID:15466863 doi:http://dx.doi.org/10.1074/jbc.C400412200
- ↑ Niwa S, Nakamura F, Tomabechi Y, Aoki M, Shigematsu H, Matsumoto T, Yamagata A, Fukai S, Hirokawa N, Goshima Y, Shirouzu M, Nitta R. Structural basis for CRMP2-induced axonal microtubule formation. Sci Rep. 2017 Sep 6;7(1):10681. doi: 10.1038/s41598-017-11031-4. PMID:28878401 doi:http://dx.doi.org/10.1038/s41598-017-11031-4
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