Constitutive activation of endocytosis by mutation of myoA, the myosin I gene of Aspergillus nidulans.
Class I myosins function in cell motility, intracellular vesicle trafficking and endocytosis. Recently, it was shown that class I myosins are phosphorylated by a member of the p21-activated kinase (PAK) family. PAK phosphorylates a conserved serine or threonine residue in the myosin heavy chain. Phosphorylation at this site is required for maximal activation of the actin-activated Mg2+-ATPase activity in vitro. This serine or threonine residue is conserved in all known class I myosins of microbial origin and in the human and mouse class VI myosins. We have investigated the in vivo significance of this phosphorylation by mutating serine 371 of the class I myosin heavy chain gene myoA of Aspergillus nidulans. Mutation to glutamic acid, which mimics phosphorylation and therefore activation of the myosin, results in an accumulation of membranes in growing hyphae. This accumulation of membranes results from an activation of endocytosis. In contrast, mutation of serine 371 to alanine had no discernible effect on endocytosis. These studies are the first to demonstrate the in vivo significance of a regulatory phosphorylation on a class I myosin. Furthermore, our results suggest that MYOA has two functions, one dependent and one independent of phosphorylation.
Yamashita
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RA
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
May
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GS
D000199:Actins / Q000494:pharmacology; D001233:Aspergillus nidulans / Q000502:physiology* / Q000648:ultrastructure; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004705:Endocytosis / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D008853:Microscopy; D016296:Mutagenesis / Q000235:genetics; D018995:Myosin Heavy Chains / Q000737:chemistry; D024461:Myosin Type I; D009218:Myosins / Q000235:genetics* / Q000502:physiology*; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015183:Restriction Mapping; D016415:Sequence Alignment; D054462:p21-Activated Kinases
D000199:Actins; D005656:Fungal Proteins; C092129:MyoA protein, Aspergillus nidulans; C089785:myosin VI; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D017301:Ca(2+) Mg(2+)-ATPase; D024461:Myosin Type I; D018995:Myosin Heavy Chains; D009218:Myosins