Axonal guidance protein FEZ1 associates with tubulin and kinesin motor protein to transport mitochondria in neurites of NGF-stimulated PC12 cells.
Fasciculation and elongation protein zeta-1 (FEZ1) promotes efficiently the neurite elongation of rat phaeochromocytoma PC12 cells. We here characterized FEZ1 in PC12 cells. Nerve growth factor (NGF) stimulation induces significant expression of endogenous FEZ1 in PC12 cells. Upon NGF stimulation FEZ1 localizes in both cytoplasm and neuritis, co-localizing with mitochondria. Silencing of FEZ1 by RNA interference efficiently reduces NGF-induced neurite elongation and the anterograde motility of mitochondria in PC12 cells. Immunoprecipitation and pulldown assay shows that FEZ1 interacts with kinesin superfamily protein 5 (KIF5) and tubulin. Thus, our results suggest that the FEZ1/kinesin complex functions for the transport of mitochondria along microtubules toward the extending neurites in differentiating PC12 cells.
Department of Structural Molecular Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
Toshitsugu
T
Fujita
Andrés D
AD
Maturana
Junko
J
Ikuta
Juri
J
Hamada
Sebastien
S
Walchli
Tadaki
T
Suzuki
Hirofumi
H
Sawa
Marie W
MW
Wooten
Toshihide
T
Okajima
Kenji
K
Tatematsu
Katsuyuki
K
Tanizawa
Shun'ichi
S
Kuroda
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D001692:Biological Transport; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D047468:Immunoprecipitation; D016547:Kinesins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014404:Tubulin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C483740:Fez1 protein, rat; D012333:RNA, Messenger; D014404:Tubulin; D020932:Nerve Growth Factor; D016547:Kinesins