PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN
PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN
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.
Carrier Proteins/genetics, Cell Cycle Proteins/genetics, Cell Line, Tumor, Centrioles/metabolism, Centrosome/metabolism, Green Fluorescent Proteins/genetics, HEK293 Cells, Humans, Microscopy, Confocal, Protein Binding, RNA Interference
Sydor, Andrew Michael
93a9eb99-194a-4251-897d-6e7776b1e304
Coyaud, Etienne
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Rovelli, Cristina
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Laurent, Estelle
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Liu, Helen
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Raught, Brian
b80f5163-ad39-46d6-9b95-2134cd4af05f
Mennella, Vito
43c60e29-c0a7-4ab8-8e5c-fcb59f70a28a
17 September 2018
Sydor, Andrew Michael
93a9eb99-194a-4251-897d-6e7776b1e304
Coyaud, Etienne
772be5a8-634a-4caa-96bd-4e878f9e59ea
Rovelli, Cristina
723dc076-1499-4662-9ab3-5447fc08570d
Laurent, Estelle
abc0a669-2bb4-4ec2-b651-ec13dcde990d
Liu, Helen
3bab8a08-d960-41c2-8d0f-c60098704471
Raught, Brian
b80f5163-ad39-46d6-9b95-2134cd4af05f
Mennella, Vito
43c60e29-c0a7-4ab8-8e5c-fcb59f70a28a
Sydor, Andrew Michael, Coyaud, Etienne, Rovelli, Cristina, Laurent, Estelle, Liu, Helen, Raught, Brian and Mennella, Vito
(2018)
PPP1R35 is a novel centrosomal protein that regulates centriole length in concert with the microcephaly protein RTTN.
eLife, 7, [e37846].
(doi:10.7554/eLife.37846).
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.
Text
elife-37846-v2
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More information
Accepted/In Press date: 31 August 2018
e-pub ahead of print date: 31 August 2018
Published date: 17 September 2018
Keywords:
Carrier Proteins/genetics, Cell Cycle Proteins/genetics, Cell Line, Tumor, Centrioles/metabolism, Centrosome/metabolism, Green Fluorescent Proteins/genetics, HEK293 Cells, Humans, Microscopy, Confocal, Protein Binding, RNA Interference
Identifiers
Local EPrints ID: 434163
URI: http://eprints.soton.ac.uk/id/eprint/434163
ISSN: 2050-084X
PURE UUID: 84468a3a-85d9-40a1-8036-cfbd0f638637
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Date deposited: 13 Sep 2019 16:30
Last modified: 16 Mar 2024 04:03
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Contributors
Author:
Andrew Michael Sydor
Author:
Etienne Coyaud
Author:
Cristina Rovelli
Author:
Estelle Laurent
Author:
Helen Liu
Author:
Brian Raught
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