The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes and regulates mitotic spindle assembly.
Microtubule behavior changes during the cell cycle and during spindle assembly. However, it remains unclear how these changes are regulated and coordinated. We describe a complex that targets the Protein Phosphatase 2A holoenzyme (PP2A) to centrosomes in C. elegans embryos. This complex includes Regulator of Spindle Assembly 1 (RSA-1), a targeting subunit for PP2A, and RSA-2, a protein that binds and recruits RSA-1 to centrosomes. In contrast to the multiple functions of the PP2A catalytic subunit, RSA-1 and RSA-2 are specifically required for microtubule outgrowth from centrosomes and for spindle assembly. The centrosomally localized RSA-PP2A complex mediates these functions in part by regulating two critical mitotic effectors: the microtubule destabilizer KLP-7 and the C. elegans regulator of spindle assembly TPXL-1. By regulating a subset of PP2A functions at the centrosome, the RSA complex could therefore provide a means of coordinating microtubule outgrowth from centrosomes and kinetochore microtubule stability during mitotic spindle assembly.
Schlaitz
Anne-Lore
AL
Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Srayko
Martin
M
Dammermann
Alexander
A
Quintin
Sophie
S
Wielsch
Natalie
N
MacLeod
Ian
I
de Robillard
Quentin
Q
Zinke
Andrea
A
Yates
John R
JR
Müller-Reichert
Thomas
T
Shevchenko
Andrei
A
Oegema
Karen
K
Hyman
Anthony A
AA
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002384:Catalysis; D018385:Centrosome / Q000378:metabolism*; D019281:Dimerization; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000166:cytology / Q000648:ultrastructure; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; C504801:TPXL-1 protein, C elegans; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D016547:Kinesins