Reference Report

Reference
Citation	Velichkova, M., Juan, J., Kadandale, P., Jean, S., Ribeiro, I., Raman, V., Stefan, C., Kiger, A.A. (2010). Drosophila Mtm and class II PI3K coregulate a PI(3)P pool with cortical and endolysosomal functions. J. Cell Biol. 190(3): 407--425. (Export to RIS)
FlyBase ID	FBrf0211470
Publication Type	Research paper
PubMed ID	20696708
PubMed Abstract	Reversible phosphoinositide phosphorylation provides a dynamic membrane code that balances opposing cell functions. However, in vivo regulatory relationships between specific kinases, phosphatases, and phosphoinositide subpools are not clear. We identified myotubularin (mtm), a Drosophila melanogaster MTM1/MTMR2 phosphoinositide phosphatase, as necessary and sufficient for immune cell protrusion formation and recruitment to wounds. Mtm-mediated turnover of endosomal phosphatidylinositol 3-phosphate (PI(3)P) pools generated by both class II and III phosphatidylinositol 3-kinases (Pi3K68D and Vps34, respectively) is needed to down-regulate membrane influx, promote efflux, and maintain endolysosomal homeostasis. Endocytosis, but not endolysosomal size, contributes to cortical remodeling by mtm function. We propose that Mtm-dependent regulation of an endosomal PI(3)P pool has separable consequences for endolysosomal homeostasis and cortical remodeling. Pi3K68D depletion (but not Vps34) rescues protrusion and distribution defects in mtm-deficient immune cells and restores functions in other tissues essential for viability. The broad interactions between mtm and class II Pi3K68D suggest a novel strategy for rebalancing PI(3)P-mediated cell functions in MTM-related human disease.
DOI	10.1083/jcb.200911020
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Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	J. Cell Biol.
Title	Journal of Cell Biology
Publication Year	1966-
ISBN/ISSN	0021-9525
Data from Reference
Aberrations (2)
	Df(2L)mtm^Δ77 Df(2L)mtm^Δ210
Alleles (25)
	Atg1^Δ3D Avic\GFP^{2x.EGFP.Scer\UAS} Avic\GFP^{Scer\UAS.T:Hsap\MYC,T:Mmus\2xFYVE} Disc\RFP^{mCherry.Scer\UAS.T:Hsap\MYC,T:Mmus\2xFYVE} Ecol\lacZ^Scer\UAS.cBa fab1^GD11899 Hsap\MTMR2^{Scer\UAS.T:Avic\GFP-EGFP} mtm^{C.Scer\UAS.T:Avic\GFP-EGFP} mtm^{dsRNA.cVa.Scer\UAS} mtm^{N.Scer\UAS.T:Avic\GFP-EGFP} mtm^{Scer\UAS.T:Disc\RFP-mCherry} mtm^z2-4747 mtm^Δ77 mtm^Δ210 Pi3K59F^KD.Scer\UAS Pi3K59F^Scer\UAS.cJa Pi3K59F^Δm22 Pi3K68D^GD7348 Pi3K68D^{Scer\UAS.T:Avic\GFP-EGFP} Pi3K68D^{Scer\UAS.T:Disc\RFP-mCherry} Rab7^{Scer\UAS.T:Avic\GFP} Scer\GAL4^Cg.PA Scer\GAL4^Pxn.PS T:Avic\GFP^EGFP T:Disc\RFP^mCherry
Constructs (18)
	P{Cg-GAL4.A} P{GD7348} P{GD11899} P{Pxn-GAL4} P{UAS-2xEGFP} P{UAS-eGFP-mtm} P{UAS-eGFP-MTMR2} P{UAS-GFP-myc-2xFYVE} P{UAS-lacZ.B} P{UAS-mCherry-mtm} P{UAS-mCherry-myc-2xFYVE} P{UAS-mCherry-Pi3K68D} P{UAS-mtm.IR} P{UAS-mtm-eGFP} P{UAS-Pi3K59F.J} P{UAS-Pi3K59F.KD} P{UAS-Pi3K68D-eGFP} P{UAS-Rab7.GFP}
Genes (18)
	Atg1 Avic\GFP CG9117 CG31643 Disc\RFP Ecol\lacZ fab1 Hsap\MTMR2 mtm Pi3K59F Pi3K68D Pi3K92E Rab5 Rab7 Rab11 Scer\GAL4 T:Hsap\MYC T:Mmus\2xFYVE
Insertions (3)
	P{EPgy2}CG9117^EY15305 P{UAS-mtm.IR}3.1 P{UAS-mtm.IR}3.5
Natural transposons (1)
	P-element