Deficiencies in the endoplasmic reticulum (ER)-membrane protein Gab1p perturb transfer of glycosylphosphatidylinositol to proteins and cause perinuclear ER-associated actin bar formation.
The essential GAB1 gene, which encodes an endoplasmic reticulum (ER)-membrane protein, was identified in a screen for mutants defective in cellular morphogenesis. A temperature-sensitive gab1 mutant accumulates complete glycosylphosphatidylinositol (GPI) precursors, and its temperature sensitivity is suppressed differentially by overexpression of different subunits of the GPI transamidase, from strong suppression by Gpi8p and Gpi17p, to weak suppression by Gaa1p, and to no suppression by Gpi16p. In addition, both Gab1p and Gpi17p localize to the ER and are in the same protein complex in vivo. These findings suggest that Gab1p is a subunit of the GPI transamidase with distinct relationships to other subunits in the same complex. We also show that depletion of Gab1p or Gpi8p, but not Gpi17p, Gpi16p, or Gaa1p causes accumulation of cofilin-decorated actin bars that are closely associated with the perinuclear ER, which highlights a functional interaction between the ER network and the actin cytoskeleton.
Grimme
Stephen J
SJ
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Gao
Xiang-Dong
XD
Martin
Paul S
PS
Tu
Kim
K
Tcheperegine
Serguei E
SE
Corrado
Kathleen
K
Farewell
Anne E
AE
Orlean
Peter
P
Bi
Erfei
E
D000199:Actins / Q000378:metabolism*; D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism; D000483:Alleles; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017353:Gene Deletion; D020043:Genes, Essential / Q000235:genetics; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D000199:Actins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000217:Acyltransferases; C081007:COOH-terminal signal transamidase