Essential role of Cenexin1, but not Odf2, in ciliogenesis.
Primary cilia are microtubule-based solitary sensing structures on the cell surface that play crucial roles in cell signaling and development. Abnormal ciliary function leads to various human genetic disorders, collectively known as ciliopathies. Outer dense fiber protein 2 (Odf2) was initially isolated as a major component of sperm-tail fibers. Subsequent studies have demonstrated the existence of many splicing variants of Odf2, including Cenexin1 (Odf2 isoform 9), which bears an unusual C-terminal extension. Strikingly, Odf2 localizes along the axoneme of primary cilia, whereas Cenexin1 localizes to basal bodies in cultured mammalian cells. Whether Odf2 and Cenexin1 contribute to primary cilia assembly by carrying out either concerted or distinct functions is unknown. By taking advantage of odf2-/- cells lacking endogenous Odf2 and Cenexin1, but exogenously expressing one or both of these proteins, we showed that Cenexin1, but not Odf2, was necessary and sufficient to induce ciliogenesis. Furthermore, the Cenexin1-dependent primary cilia assembly pathway appeared to function independently of Odf2. Consistently, Cenexin1, but not Odf2, interacted with GTP-loaded Rab8a, localized to the distal/subdistal appendages of basal bodies, and facilitated the recruitment of Chibby, a centriolar component that is important for proper ciliogenesis. Taken together, our results suggest that Cenexin1 plays a critical role in ciliogenesis through its C-terminal extension that confers a unique ability to mediate primary cilia assembly. The presence of multiple splicing variants hints that the function of Odf2 is diversified in such a way that each variant has a distinct role in the complex cellular and developmental processes.
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Jaerak
J
Chang
Sang Gwon
SG
Seo
Kyung Ho
KH
Lee
Kunio
K
Nagashima
Jeong K
JK
Bang
Bo Yeon
BY
Kim
Raymond L
RL
Erikson
Ki-Won
KW
Lee
Hyong Joo
HJ
Lee
Jung-Eun
JE
Park
Kyung S
KS
Lee
D017398:Alternative Splicing; D000818:Animals; D054468:Axoneme / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002502:Centrioles / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C517894:Chibby protein, mouse; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; C490106:Odf2 protein, mouse; D020033:Protein Isoforms; C546061:Rab8a protein, mouse; D020691:rab GTP-Binding Proteins
Cenexin1; Chibby; Odf2; Rab8a; ciliogenesis; primary cilia