RRC ID 32712
著者 Hoeller O, Bolourani P, Clark J, Stephens LR, Hawkins PT, Weiner OD, Weeks G, Kay RR.
タイトル Two distinct functions for PI3-kinases in macropinocytosis.
ジャーナル J Cell Sci
Abstract Class-1 PI3-kinases are major regulators of the actin cytoskeleton, whose precise contributions to chemotaxis, phagocytosis and macropinocytosis remain unresolved. We used systematic genetic ablation to examine this question in growing Dictyostelium cells. Mass spectroscopy shows that a quintuple mutant lacking the entire genomic complement of class-1 PI3-kinases retains only 10% of wild-type PtdIns(3,4,5)P3 levels. Chemotaxis to folate and phagocytosis of bacteria proceed normally in the quintuple mutant but macropinocytosis is abolished. In this context PI3-kinases show specialized functions, only one of which is directly linked to gross PtdIns(3,4,5)P3 levels: macropinosomes originate in patches of PtdIns(3,4,5)P3, with associated F-actin-rich ruffles, both of which depend on PI3-kinase 1/2 (PI3K1/2) but not PI3K4, whereas conversion of ruffles into vesicles requires PI3K4. A biosensor derived from the Ras-binding domain of PI3K1 suggests that Ras is activated throughout vesicle formation. Binding assays show that RasG and RasS interact most strongly with PI3K1/2 and PI3K4, and single mutants of either Ras have severe macropinocytosis defects. Thus, the fundamental function of PI3-kinases in growing Dictyostelium cells is in macropinocytosis where they have two distinct functions, supported by at least two separate Ras proteins.
巻・号 126(Pt 18)
ページ 4296-307
公開日 2013-9-15
DOI 10.1242/jcs.134015
PII jcs.134015
PMID 23843627
PMC PMC3772393
MeSH Actins / genetics Actins / metabolism* Chemotaxis Humans Phagocytosis Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Pinocytosis / genetics* Signal Transduction
IF 4.573
引用数 48
WOS 分野 CELL BIOLOGY
リソース情報
細胞性粘菌 G24196