title: Disparate Regulatory Mechanisms Control Fat3 and P75NTR Protein Transport through a Conserved Kif5-Interaction Domain.
abstract: Directed transport delivers proteins to specific cellular locations and is one mechanism by which cells establish and maintain polarized cellular architectures. The atypical cadherin Fat3 directs the polarized extension of dendrites in retinal amacrine cells by influencing the distribution of cytoskeletal regulators during retinal development, however the mechanisms regulating the distribution of Fat3 remain unclear. We report a novel Kinesin/Kif5 Interaction domain (Kif5-ID) in Fat3 that facilitates Kif5B binding, and determines the distribution of Fat3 cytosolic domain constructs in neurons and MDCK cells. The Kif5-ID sequence is conserved in the neurotrophin receptor P75NTR, which also binds Kif5B, and Kif5-ID mutations similarly result in P75NTR mislocalization. Despite these similarities, Kif5B-mediated protein transport is differentially regulated by these two cargos. For Fat3, the Kif5-ID is regulated by alternative splicing, and the timecourse of splicing suggests that the distribution of Fat3 may switch between early and later stages of retinal development. In contrast, P75NTR binding to Kif5B is enhanced by tyrosine phosphorylation and thus has the potential to be dynamically regulated on a more rapid time scale.
authors: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors: Haixia
authors: H
authors: Cheng
authors: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors: Jessica
authors: J
authors: Burroughs-Garcia
authors: Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Jacqueline E
authors: JE
authors: Birkness
authors: Department of Chemistry, Indiana University, Bloomington, Indiana, United States of America.
authors: Jonathan C
authors: JC
authors: Trinidad
authors: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.|Department of Neurobiology & Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors: Michael R
authors: http://orcid.org/0000-0001-6319-7945
authors: MR
authors: Deans
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D015820:Cadherins; C448779:FAT3 protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D004815:Epidermal Growth Factor; D016547:Kinesins