Ankyrin repeat-rich membrane spanning/Kidins220 protein interacts with mammalian Septin 5.
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.
Park
Han Jeong
HJ
Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Park
Hwan-Woo
HW
Lee
Shin-Jae
SJ
Arevalo
Juan Carlos
JC
Park
Young-Seok
YS
Lee
Seung-Pyo
SP
Paik
Ki-Suk
KS
Chao
Moses V
MV
Chang
Mi-Sook
MS
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*
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