A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.
Primary cilium dysfunction affects the development and homeostasis of many organs in Bardet-Biedl syndrome (BBS). We recently showed that seven highly conserved BBS proteins form a stable complex, the BBSome, that functions in membrane trafficking to and inside the primary cilium. We have now discovered a BBSome subunit that we named BBIP10. Similar to other BBSome subunits, BBIP10 localizes to the primary cilium, BBIP10 is present exclusively in ciliated organisms, and depletion of BBIP10 yields characteristic BBS phenotypes in zebrafish. Unexpectedly, BBIP10 is required for cytoplasmic microtubule polymerization and acetylation, two functions not shared with any other BBSome subunits. Strikingly, inhibition of the tubulin deacetylase HDAC6 restores microtubule acetylation in BBIP10-depleted cells, and BBIP10 physically interacts with HDAC6. BBSome-bound BBIP10 may therefore function to couple acetylation of axonemal microtubules and ciliary membrane growth.
Loktev
Alexander V
AV
Genentech, Inc., South San Francisco, CA 94080, USA.
Zhang
Qihong
Q
Beck
John S
JS
Searby
Charles C
CC
Scheetz
Todd E
TE
Bazan
J Fernando
JF
Slusarski
Diane C
DC
Sheffield
Val C
VC
Jackson
Peter K
PK
Nachury
Maxence V
MV
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000502:physiology*
D002352:Carrier Proteins; D029961:Zebrafish Proteins; C534297:bbip1 protein, zebrafish; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases