title: CRMP4 and CRMP2 Interact to Coordinate Cytoskeleton Dynamics, Regulating Growth Cone Development and Axon Elongation.
abstract: Cytoskeleton dynamics are critical phenomena that underpin many fundamental cellular processes. Collapsin response mediator proteins (CRMPs) are highly expressed in the developing nervous system, mediating growth cone guidance, neuronal polarity, and axonal elongation. However, whether and how CRMPs associate with microtubules and actin coordinated cytoskeletal dynamics remain unknown. In this study, we demonstrated that CRMP2 and CRMP4 interacted with tubulin and actin in vitro and colocalized with the cytoskeleton in the transition-zone in developing growth cones. CRMP2 and CRMP4 also interacted with one another coordinately to promote growth cone development and axonal elongation. Genetic silencing of CRMP2 enhanced, whereas overexpression of CRMP2 suppressed, the inhibitory effects of CRMP4 knockdown on axonal development. In addition, knockdown of CRMP2 or overexpression of truncated CRMP2 reversed the promoting effect of CRMP4. With the overexpression of truncated CRMP2 or CRMP4 lacking the cytoskeleton interaction domain, the promoting effect of CRMP was suppressed. These data suggest a model in which CRMP2 and CRMP4 form complexes to bridge microtubules and actin and thus work cooperatively to regulate growth cone development and axonal elongation.
authors.affiliation: Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China ; Postdoctoral Stations of Integrated Traditional and Western Medicine, Medical College of Jinan University, Guangzhou 510630, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China ; Department of Pediatrics, Guangzhou Women and Children's Medical Center, The Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Caihui
authors.initials: C
authors.lastname: Cha
authors.affiliation: Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China ; Postdoctoral Stations of Integrated Traditional and Western Medicine, Medical College of Jinan University, Guangzhou 510630, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China ; Department of Pediatrics, Guangzhou Women and Children's Medical Center, The Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Sitang
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China ; Department of Pathophysiology, Medical College of Jinan University, Guangzhou 510630, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Guo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; C449760:Dpysl3 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; C095114:collapsin response mediator protein-2