PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN.

ELife
Andrew Michael SydorVito Mennella

Abstract

Centrosome structure, function, and number are finely regulated at the cellular level to ensure normal mammalian development. Here, we characterize PPP1R35 as a novel bona fide centrosomal protein and demonstrate that it is critical for centriole elongation. Using quantitative super-resolution microscopy mapping and live-cell imaging we show that PPP1R35 is a resident centrosomal protein located in the proximal lumen above the cartwheel, a region of the centriole that has eluded detailed characterization. Loss of PPP1R35 function results in decreased centrosome number and shortened centrioles that lack centriolar distal and microtubule wall associated proteins required for centriole elongation. We further demonstrate that PPP1R35 acts downstream of, and forms a complex with, RTTN, a microcephaly protein required for distal centriole elongation. Altogether, our study identifies a novel step in the centriole elongation pathway centered on PPP1R35 and elucidates downstream partners of the microcephaly protein RTTN.

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Citations

Sep 20, 2018·Molecular Biology of the Cell·Chii Shyang FongMeng-Fu Bryan Tsou
Jul 13, 2019·Cells·Vladimir Joukov, Arcangela De Nicolo
Jun 7, 2020·Cells·Melis Dilara ArslanhanElif Nur Firat-Karalar
Jun 17, 2020·The Journal of Cell Biology·Pallavi PandaDavid M Glover
Sep 30, 2020·Cells·Rustem E Uzbekov, Tomer Avidor-Reiss
Feb 4, 2021·The Journal of Cell Biology·Yuan TianJingyan Fu
Nov 22, 2020·Current Opinion in Structural Biology·Ashwani SharmaMichel O Steinmetz
Nov 2, 2020·Current Opinion in Structural Biology·Raksha DeviSuzanna L Prosser
Aug 19, 2020·Molecular and Cellular Endocrinology·Tomer Avidor-ReissEmily Lillian Fishman
Jan 9, 2022·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Yuan TianJingyan Fu

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Datasets Mentioned

BETA
KIAA0753

Methods Mentioned

BETA
fluorescence microscopy
confocal microscopy
Fluorescence recovery after photobleaching
super-resolution
fluorescence imaging
PCR
immunoprecipitation
co-IP
acetylation
transfection

Software Mentioned

Clustal Omega
3DSIM
Fiji
ImageJ
Zeiss Zen Black
MrBayes
ZEN Black
Leica Analysis Suite X
ProteinProphet
Delta Blastp

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