SAS-1 is a C2 domain protein critical for centriole integrity in C. elegans

Lukas von Tobel; Tamara Mikeladze-Dvali; Marie Delattre; Fernando R Balestra; Simon Blanchoud; Susanne Finger; Graham Knott; Thomas Müller-Reichert; Pierre Gönczy

doi:10.1371/journal.pgen.1004777

SAS-1 is a C2 domain protein critical for centriole integrity in C. elegans

PLoS Genet. 2014 Nov 20;10(11):e1004777. doi: 10.1371/journal.pgen.1004777. eCollection 2014 Nov.

Authors

Lukas von Tobel¹, Tamara Mikeladze-Dvali¹, Marie Delattre¹, Fernando R Balestra¹, Simon Blanchoud¹, Susanne Finger², Graham Knott³, Thomas Müller-Reichert⁴, Pierre Gönczy¹

Affiliations

¹ Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
² Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, Switzerland.
³ BioEM Facility, School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
⁴ Structural Cell Biology Group, Experimental Center, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Abstract

Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sperm cells, where such integrity is particularly critical. We identified C. elegans sas-1 in a genetic screen as a locus required for bipolar spindle assembly in the early embryo. Our analysis reveals that sperm-derived sas-1 mutant centrioles lose their integrity shortly after fertilization, and that a related defect occurs when maternal sas-1 function is lacking. We establish that sas-1 encodes a C2 domain containing protein that localizes to centrioles in C. elegans, and which can bind and stabilize microtubules when expressed in human cells. Moreover, we uncover that SAS-1 is related to C2CD3, a protein required for complete centriole formation in human cells and affected in a type of oral-facial-digital (OFD) syndrome.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / growth & development
Cell Line
Centrioles / genetics*
Centrioles / metabolism
Centrosome / metabolism
Cilia / genetics
Cilia / physiology
Embryo, Nonmammalian
Flagella / genetics
Flagella / physiology
Gene Expression Regulation, Developmental
Humans
Male
Microtubule-Associated Proteins / biosynthesis
Microtubule-Associated Proteins / genetics*
Microtubules / genetics
Microtubules / metabolism*
Spermatozoa / growth & development
Spermatozoa / metabolism

Substances

C2cd3 protein, human
Microtubule-Associated Proteins

Grants and funding

This work was supported by a doctoral fellowship from the Boehringer Ingelheim Fonds to LvT, by post-doctoral fellowships from EMBO (ALTF 237-2007) and from the Human Frontiers Science Program (LT01017/2008-L) to TMD, by post-doctoral fellowships from EMBO (ALTF 98-2001) and the Roche Research Foundation (161-2004) to MD, as well as a grant from the ERC to PG (AdG 233335). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.