title: FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular plate and regulate actin polymerization in vitro.
abstract: Mammalian FCHSD1 and FCHSD2 are homologous proteins containing an amino-terminal F-BAR domain and two SH3 domains near their carboxyl-termini. We report here that FCHSD1 and FCHSD2 are expressed in mouse cochlear sensory hair cells. FCHSD1 mainly localizes to the cuticular plate, whereas FCHSD2 mainly localizes along the stereocilia in a punctuate pattern. Nervous Wreck (Nwk), the Drosophila ortholog of FCHSD1 and FCHSD2, has been shown to bind Wsp and play an important role in F-actin assembly. We show that, like its Drosophila counterpart, FCHSD2 interacts with WASP and N-WASP, the mammalian orthologs of Drosophila Wsp, and stimulates F-actin assembly in vitro. In contrast, FCHSD1 doesn't bind WASP or N-WASP, and can't stimulate F-actin assembly when tested in vitro. We found, however, that FCHSD1 binds via its F-BAR domain to the SH3 domain of Sorting Nexin 9 (SNX9), a well characterized BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization. FCHSD1 greatly enhances SNX9's WASP-Arp2/3-dependent F-actin polymerization activity. In hair cells, SNX9 was detected in the cuticular plate, where it colocalizes with FCHSD1. Our results suggest that FCHSD1 and FCHSD2 could modulate F-actin assembly or maintenance in hair cell stereocilia and cuticular plate.
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
authors: Huiren
authors: H
authors: Cao
authors: Xiaolei
authors: X
authors: Yin
authors: Yujie
authors: Y
authors: Cao
authors: Yecheng
authors: Y
authors: Jin
authors: Shan
authors: S
authors: Wang
authors: Yanhui
authors: Y
authors: Kong
authors: Yuexing
authors: Y
authors: Chen
authors: Jiangang
authors: J
authors: Gao
authors: Stefan
authors: S
authors: Heller
authors: Zhigang
authors: Z
authors: Xu
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D059547:Stereocilia / Q000378:metabolism / Q000648:ultrastructure; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D000199:Actins; D002352:Carrier Proteins; C495298:FCHSD1 protein, human; C479761:FCHSD2 protein, human; D008565:Membrane Proteins; C495772:Wasl protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal