Analysis of phosphoinositide binding domain properties within the myotubularin-related protein MTMR3

Lorenzo, Óscar; Urbé, Sylvie; Clague, Michael J.

doi:10.1242/jcs.02325

Cited by 69 publications

(72 citation statements)

References 50 publications

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“…These widely distributed phosphatases are characterized by the presence of a FYVE domain in their extended COOH termini (1659,1814). Interestingly, however, the FYVE domain of MTMR3 does not bind PtdIns3P, nor is it responsible for the endosomal localization of MTMR3 (941). MTMR3, on the other hand, binds PtdIns5P at its GRAM domain (941), which may be important for allosteric activation of the enzyme by this rare lipid species (1355).…”

Section: Myotubularinsmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,359

1,655

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Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

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Section: Myotubularinsmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,359

1,655

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“…R*, photoactivated rhodopsin; Grb14, growth factor receptor-bound protein 14; IR, insulin receptor; PTP1B, protein tyrosine phosphatase; Y-P, phosphotyrosine. (166)(167)(168)(169)(170). We applied this approach to an in vivo model of transgenic frogs and found light-dependent generation of 3 ′ -phosphoinositides specifi cally in photoreceptor cells using the Akt1-AH domain as the cellular probe ( 61 ).…”

Section: Light-induced Activation Of Pi3k Pathway In Rod Photoreceptomentioning

confidence: 99%

Phosphoinositide 3-kinase signaling in the vertebrate retina

Rajala

2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org was established by Streb et al. ( 3 ) in their classic paper that showed elevations in IP 3 caused intracellular release of bound calcium. Subsequently, 1,2-DG was found to stimulate protein kinase C (PKC), a serine/threonine kinase that phosphorylates a number of cellular proteins ( 4 ). Activation of the PLC/PKC cascade affects a variety of cellular events, including secretion, phagocytosis, smooth muscle contraction, proliferation, neurotransmission, and metabolism [see reviews by Rhee ( 5 ), Rhee and Choi ( 6 ), and Berridge ( 7 ) THE PI CYCLEIn the early 1950s, Hokin and Hokin ( 1, 2 ) discovered that addition of acetylcholine to brain slices stimulated the incorporation of phosphate and inositol but not glycerol into lipids; the major products of this incorporation were phosphatidylinositol (PI) and phosphatidic acid. Subsequent studies defi ned the reactions of the PI cycle and showed that the initial event was receptor-meditated activation of a phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PI-4,5-P 2 ) to 1,2-diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP 3 ). This increase in lipid synthesis reported by the Hokins was a recovery reaction that rapidly replenished PI separate from de novo PI synthesis. The role of 1,4, This work was supported by grants

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“…MTMR4 contains an Nterminal PH-GRAM domain, a central myotubularin homology region (MTMHR) and a coiled-coil motif followed by a C-terminal FYVE domain (Zhao et al, 2001;Robinson and Dixon, 2006). In MTMR3, the PH domain binds PtdIns(5)P and perhaps PtdIns(3,5)P 2 , and MTMR3 localizes to the cytosol and, under some conditions, to the endoplasmic reticulum and/or the Golgi (Walker et al, 2001;Lorenzo et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The myotubularin phosphatase MTMR4 regulates sorting from early endosomes

Naughtin

Sheffield

Rahman

et al. 2010

Journal of Cell Science

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SummaryPhosphatidylinositol 3-phosphate [PtdIns(3)P] regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11-and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4C407A , the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of MTMR4 C407A , which acts as a dominant-negative construct, significantly accelerated Tfn recycling. However, in MTMR4 knockdown cells Tfn recycling was unchanged, suggesting that other MTMs might also contribute to recycling. MTMR4 regulated the subcellular distribution of Rab11 and, in cells with RNAi-mediated knockdown of MTMR4, Rab11 was directed away from the pericentriolar recycling compartment. The subcellular distribution of VAMP3, a v-SNARE protein that resides in recycling endosomes and endosomederived transport vesicles, was also regulated by MTMR4. Therefore, MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway.

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Analysis of phosphoinositide binding domain properties within the myotubularin-related protein MTMR3

Cited by 69 publications

References 50 publications

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Phosphoinositide 3-kinase signaling in the vertebrate retina

The myotubularin phosphatase MTMR4 regulates sorting from early endosomes

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