title: Functional Coordination of WAVE and WASP in C. elegans Neuroblast Migration.
abstract: Directional cell migration is critical for metazoan development. We define two molecular pathways that activate the Arp2/3 complex during neuroblast migration in Caenorhabditis elegans. The transmembrane protein MIG-13/Lrp12 is linked to the Arp2/3 nucleation-promoting factors WAVE or WASP through direct interactions with ABL-1 or SEM-5/Grb2, respectively. WAVE mutations partially impaired F-actin organization and decelerated cell migration, and WASP mutations did not inhibit cell migration but enhanced migration defects in WAVE-deficient cells. Purified SEM-5 and MIG-2 synergistically stimulated the F-actin branching activity of WASP-Arp2/3 in vitro. In GFP knockin animals, WAVE and WASP were largely organized into separate clusters at the leading edge, and the amount of WASP was less than WAVE but could be elevated by WAVE mutations. Our results indicate that the MIG-13-WAVE pathway provides the major force for directional cell motility, whereas MIG-13-WASP partially compensates for its loss, underscoring their coordinated activities in facilitating robust cell migration.
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Zhiwen
authors: Z
authors: Zhu
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Yongping
authors: Y
authors: Chai
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Yuxiang
authors: Y
authors: Jiang
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Wenjing
authors: W
authors: Li
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Huifang
authors: H
authors: Hu
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Wei
authors: W
authors: Li
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Jia-Wei
authors: JW
authors: Wu
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Zhi-Xin
authors: ZX
authors: Wang
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
authors: Shanjin
authors: S
authors: Huang
authors: Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China. Electronic address: guangshuoou@tsinghua.edu.cn.
authors: Guangshuo
authors: G
authors: Ou
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002465:Cell Movement; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D029742:Caenorhabditis elegans Proteins; C120452:MIG-13 protein, Caenorhabditis elegans; D008565:Membrane Proteins; C085751:Sem-5 protein, C elegans; C516680:ABL-1 protein, C elegans; D016315:Proto-Oncogene Proteins c-abl
keywords: ABL-1; Arp2/3; MIG-13/LRP12; SEM-5/Grb2; WASP; WAVE; cell migration; cytoskeleton