title: SAS-1 is a C2 domain protein critical for centriole integrity in C. elegans.
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.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: von Tobel
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Tamara
authors.initials: T
authors.lastname: Mikeladze-Dvali
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Delattre
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Balestra
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Blanchoud
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Finger
authors.affiliation: BioEM Facility, School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Graham
authors.initials: G
authors.lastname: Knott
authors.affiliation: Structural Cell Biology Group, Experimental Center, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller-Reichert
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL) Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D002460:Cell Line; D002502:Centrioles / Q000235:genetics* / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D002923:Cilia / Q000235:genetics / Q000502:physiology; D004625:Embryo, Nonmammalian; D005407:Flagella / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism
chemical_list: C000594350:C2cd3 protein, human; D008869:Microtubule-Associated Proteins