Other
-
Scientific MembershipsEuropean Molecular BIology Organization
Publications (214) View all
-
Article: Spatiotemporal control of Cindr at ring canals during incomplete cytokinesis in the Drosophila male germline.
[show abstract] [hide abstract]
ABSTRACT: During male and female gametogenesis in species ranging from insects to mammals, germ cell cyst formation by incomplete cytokinesis involves the stabilization of cleavage furrows and the formation of stable intercellular bridges called ring canals. Accurate regulation of incomplete cytokinesis is required for both female and male fertility in Drosophila melanogaster. Nevertheless, the molecular mechanisms controlling complete versus incomplete cytokinesis are largely unknown. Here, we show that the scaffold protein Cindr is a novel component of both mitotic and meiotic ring canals during Drosophila spermatogenesis. Strikingly, unlike other male germline ring canal components, including Anillin and Pavarotti, Cindr and contractile ring F-actin dissociate from mitotic ring canals and translocate to the fusome upon completion of the mitotic germ cell divisions. We provide evidence that the loss of Cindr from mitotic ring canals is coordinated by signals that mediate the transition from germ cell mitosis to differentiation. Interestingly, Cindr loss from ring canals coincides with completion of the mitotic germ cell divisions in both Drosophila females and males, thus marking a common step of gametogenesis. We also show that Cindr co-localizes with Anillin at mitotic and meiotic ring canals and is recruited to the contractile ring by Anillin during male germ cell meiotic cytokinesis. Taken together, our analyses reveal a key step of incomplete cytokinesis at the endpoint of the mitotic germ cell divisions in D. melanogaster.Developmental Biology 03/2013; · 4.07 Impact Factor -
Article: Class III phosphatidylinositol 3-kinase and its catalytic product PtdIns3P in regulation of endocytic membrane traffic.
[show abstract] [hide abstract]
ABSTRACT: Endocytosis and subsequent membrane traffic through endosomes are cellular processes that are integral to eukaryotic evolution, and numerous human diseases are associated with their dysfunctions. Consequently, it is important to untangle the molecular machineries that regulate membrane dynamics and protein flow in the endocytic pathway. Central in this context is class III phosphatidylinositol 3-kinase (PI3K-III), an evolutionarily conserved enzyme complex that phosphorylates phosphatidylinositol into phosphatidylinositol 3-phosphate (PtdIns3P). PtdIns3P recruits specific effector proteins, most of which contain FYVE or PX domains, to promote endocytosis, endosome fusion, endosome motility, and endosome maturation, as well as cargo sorting to lysosomes, the biosynthetic pathway or the plasma membrane. Here we review the functions of key PtdIns3P effectors in regulation of endocytic membrane dynamics and protein sorting. © 2013 The Authors Journal compilation © 2013 FEBS.FEBS Journal 01/2013; · 3.79 Impact Factor -
Article: Antibody crossreactivity between the tumour suppressor PHLPP1 and the proto-oncogene β-catenin.
EMBO Reports 12/2012; · 7.36 Impact Factor -
Article: Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration.
[show abstract] [hide abstract]
ABSTRACT: Although phosphatidylinositol 5-phosphate (PtdIns5P) is present in many cell types and its biogenesis is increased by diverse stimuli, its precise cellular function remains elusive. Here we show that PtdIns5P levels increase when cells are stimulated to move and we find PtdIns5P to promote cell migration in tissue culture and in a Drosophila in vivo model. First, class III phosphatidylinositol 3-kinase, which produces PtdIns3P, was shown to be involved in migration of fibroblasts. In a cell migration screen for proteins containing PtdIns3P-binding motifs, we identified the phosphoinositide 5-kinase PIKfyve and the phosphoinositide 3-phosphatase MTMR3, which together constitute a phosphoinositide loop that produces PtdIns5P via PtdIns(3,5)P(2). The ability of PtdIns5P to stimulate cell migration was demonstrated directly with exogenous PtdIns5P and a PtdIns5P-producing bacterial enzyme. Thus, the identified phosphoinositide loop defines a new role for PtdIns5P in cell migration.EMBO Reports 11/2012; · 7.36 Impact Factor -
Article: The PtdIns3P-Binding Protein Phafin 2 Mediates Epidermal Growth Factor Receptor Degradation by Promoting Endosome Fusion.
[show abstract] [hide abstract]
ABSTRACT: Phosphatidylinositol 3-phosphate (PtdIns3P) orchestrates endosomal cargo transport, fusion and motility by recruiting FYVE or PX domain-containing effector proteins to endosomal membranes. In an attempt to discover novel PtdIns3P effectors involved in the termination of growth factor receptor signalling, we performed an siRNA screen for epidermal growth factor (EGF) degradation, targeting FYVE and PX domain proteins in the human proteome. This screen identified several potential regulators of EGF degradation, including HRS (used as positive control), PX kinase, MTMR4 and Phafin2/PLEKHF2. As Phafin2 has not previously been shown to be required for EGF receptor (EGFR) degradation, we performed further functional studies on this protein. Loss of Phafin2 was found to decrease early endosome size, whereas overexpression of Phafin2 resulted in enlarged endosomes. Moreover, both the EGFR and the fluid-phase marker dextran were retained in abnormally small endosomes in Phafin2-depleted cells. In yeast two-hybrid analysis we identified Phafin2 as a novel interactor of the endosomal-tethering protein EEA1, and Phafin2 colocalized strongly with EEA1 in microdomains of the endosome membrane. Our results suggest that Phafin2 controls receptor trafficking and fluid-phase transport through early endosomes by facilitating endosome fusion in concert with EEA1.Traffic 07/2012; 13(11):1547-63. · 4.92 Impact Factor
