TY - JOUR
T1 - The small GTPase RSG1 controls a final step in primary cilia initiation
AU - Agbu, Stephanie O.
AU - Liang, Yinwen
AU - Liu, Aimin
AU - Anderson, Kathryn V.
N1 - Funding Information:
We thank Heather Alcorn for assistance with exome sequencing and Kunihiro Uryu (Rockefeller Electron Microscopy Core) and Nina Lampen (MSK CC Electron Microscopy Core) for assistance with transmission and scanning electron microscopy, respectively. We also thank the Rockefeller Bio-Imaging Resource Center and MSK CC Molecular Cytology Facility (Y. Romin, S. Fujisawa, and V. Boyko) for assistance with wide-field and confocal microscopy, respectively. We thank Peter Romanienko (MSK CC Mouse Genetics Core) for assistance with generating CRI SPR mice and the Genomics Core Facility and Nicholas Socci (MSK CC Bioinformatics Core) for assistance in processing whole-exome sequencing data. We thank Ronald Roepman and Christopher Westlake for tagged constructs. We thank Devanshi Jain (MSK CC) and Greg Pazour (University of Massachusetts) for the help with qPCR experiments. We are grateful to Angela Parrish, Rocío Hernández-Martinez, and Benjamin Cyge for comments on the manuscript. The work was supported by the National Institutes of Health (R37 HD03455 and R01 NS044385 to K.V. Anderson), a Memorial Sloan Kettering Cancer Center Support Grant (P30 CA008748), and a National Institutes of Health training grant (T32 HD060600) to S.O. Agbu. The authors declare no competing financial interests.
Funding Information:
The work was supported by the National Institutes of Health (R37 HD03455 and R01 NS044385 to K.V. Anderson), a Memorial Sloan Kettering Cancer Center Support Grant (P30 CA008748), and a National Institutes of Health training grant (T32 HD060600) to S.O. Agbu. The authors declare no competing financial interests.
Publisher Copyright:
© 2018 Agbu et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Primary cilia, which are essential for normal development and tissue homeostasis, are extensions of the mother centriole, but the mechanisms that remodel the centriole to promote cilia initiation are poorly understood. Here we show that mouse embryos that lack the small guanosine triphosphatase RSG1 die at embryonic day 12.5, with developmental abnormalities characteristic of decreased cilia-dependent Hedgehog signaling. Rsg1 mutant embryos have fewer primary cilia than wild-type embryos, but the cilia that form are of normal length and traffic Hedgehog pathway proteins within the cilium correctly. Rsg1 mother centrioles recruit proteins required for cilia initiation and dock onto ciliary vesicles, but axonemal microtubules fail to elongate normally. RSG1 localizes to the mother centriole in a process that depends on tau tubulin kinase 2 (TTBK2), the CPL ANE complex protein Inturned (INTU), and its own GTPase activity. The data suggest a specific role for RSG1 in the final maturation of the mother centriole and ciliary vesicle that allows extension of the ciliary axoneme.
AB - Primary cilia, which are essential for normal development and tissue homeostasis, are extensions of the mother centriole, but the mechanisms that remodel the centriole to promote cilia initiation are poorly understood. Here we show that mouse embryos that lack the small guanosine triphosphatase RSG1 die at embryonic day 12.5, with developmental abnormalities characteristic of decreased cilia-dependent Hedgehog signaling. Rsg1 mutant embryos have fewer primary cilia than wild-type embryos, but the cilia that form are of normal length and traffic Hedgehog pathway proteins within the cilium correctly. Rsg1 mother centrioles recruit proteins required for cilia initiation and dock onto ciliary vesicles, but axonemal microtubules fail to elongate normally. RSG1 localizes to the mother centriole in a process that depends on tau tubulin kinase 2 (TTBK2), the CPL ANE complex protein Inturned (INTU), and its own GTPase activity. The data suggest a specific role for RSG1 in the final maturation of the mother centriole and ciliary vesicle that allows extension of the ciliary axoneme.
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U2 - 10.1083/jcb.201604048
DO - 10.1083/jcb.201604048
M3 - Article
C2 - 29038301
AN - SCOPUS:85039852328
SN - 0021-9525
VL - 217
SP - 413
EP - 427
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -