title: Ankyrin repeat-rich membrane spanning/Kidins220 protein interacts with mammalian Septin 5.
abstract: Neurotrophin receptors utilize specific adaptor proteins to activate signaling pathways involved in various neuronal functions, such as neurite outgrowth and cytoskeletal remodeling. The Ankyrin-Repeat Rich Membrane Spanning (ARMS)/kinase D-interacting substrate-220 kDa (Kidins220) serves as a unique downstream adaptor protein of Trk receptor tyrosine kinases. To gain insight into the role of ARMS/Kidins220, a yeast two-hybrid screen of a rat dorsal root ganglion library was performed using the C-terminal region of ARMS/Kidins220 as bait. The screen identified a mammalian septin, Septin 5 (Sept5), as an interacting protein. Co-immunoprecipitation using lysates from transiently transfected HEK-293 cells revealed the specific interaction between ARMS/Kidins220 and Sept5. Endogenous ARMS/Kidins220 and Sept5 proteins were colocalized in primary hippocampal neurons and were also predominantly expressed at the plasma membrane and in the tips of growing neurites in nerve growth factor-treated PC12 cells. Mapping of Sept5 domains important for ARMS/Kidins220 binding revealed a highly conserved N-terminal region of Sept5. The direct interaction between ARMS/Kidins220 and Sept5 suggests a possible role of ARMS/Kidins220 as a functional link between neurotrophin receptors and septins to mediate neurotrophin-induced intracellular signaling events, such as neurite outgrowth and cytoskeletal remodeling.
authors.affiliation: Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
authors.forename: Han Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Hwan-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Shin-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Arevalo
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Park
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Lee
authors.forename: Ki-Suk
authors.initials: KS
authors.lastname: Paik
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D017353:Gene Deletion; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D058112:Septins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; C418610:Kidins220 protein, rat; D008565:Membrane Proteins; D010750:Phosphoproteins; D020932:Nerve Growth Factor; C491613:Septin5 protein, rat; D058112:Septins