title: Phosphorylation-dependent activation of peroxisome proliferator protein PEX11 controls peroxisome abundance.
abstract: Peroxisomes are dynamic organelles that divide continuously in growing cell cultures and expand extensively in lipid-rich medium. Peroxisome population control is achieved in part by Pex11p-dependent regulation of peroxisome size and number. Although the production of Pex11p in yeast is tightly linked to peroxisome biogenesis by transcriptional regulation of the PEX11 gene, it remains unclear if and how Pex11p activity could be modulated by rapid signaling. We report the reversible phosphorylation of Saccharomyces cerevisiae Pex11p in response to nutritional cues and delineate a mechanism for phosphorylation-dependent activation of Pex11p through the analysis of phosphomimicking mutants. Peroxisomal phenotypes in the PEX11-A and PEX11-D strains expressing constitutively dephosphorylated and phosphorylated forms of Pex11p resemble those of PEX11 gene knock-out and overexpression mutants, although PEX11 transcript and Pex11 protein levels remain unchanged. We demonstrate functional inequality and differences in subcellular localization of the Pex11p forms. Pex11Dp promotes peroxisome fragmentation when reexpressed in cells containing induced peroxisomes. Pex11p translocates between endoplasmic reticulum and peroxisomes in a phosphorylation-dependent manner, whereas Pex11Ap and Pex11Dp are impaired in trafficking and constitutively associated with mature and proliferating peroxisomes, respectively. Overexpression of cyclin-dependent kinase Pho85p results in hyperphosphorylation of Pex11p and peroxisome proliferation. This study provides the first evidence for control of peroxisome dynamics by phosphorylation-dependent regulation of a peroxin.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Knoblach
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rachubinski
mesh_terms: D004721:Endoplasmic Reticulum; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D000074401:Peroxins; D020675:Peroxisomes / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D012333:RNA, Messenger / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C092128:PEX11 protein, S cerevisiae; D000074401:Peroxins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins