MyosinV controls PTEN function and neuronal cell size

Michiel T. van Diepen; Maddy Parsons; C. Peter Downes; Nicholas R. Leslie; Robert Hindges; Britta J. Eickholt

doi:10.1038/ncb1961

MyosinV controls PTEN function and neuronal cell size

Michiel T. van Diepen, Maddy Parsons, C. Peter Downes, Nicholas R. Leslie, Robert Hindges, Britta J. Eickholt

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Abstract

The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types(1). PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P-3 to PtdIns(4,5)P-2, thereby antagonizing PI(3) K (phosphoinositide 3-kinase) and its established downstream effector pathways(2). However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P-3 (refs 3-5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Forster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss(6,7), required PI(3) K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

Original language	English
Pages (from-to)	1191 - 1196
Number of pages	6
Journal	Nature Cell Biology
Volume	11
Issue number	10
DOIs	https://doi.org/10.1038/ncb1961
Publication status	Published - 2009

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@article{27d9922a98894639a4c6221914ece875,

title = "MyosinV controls PTEN function and neuronal cell size",

abstract = "The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types(1). PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P-3 to PtdIns(4,5)P-2, thereby antagonizing PI(3) K (phosphoinositide 3-kinase) and its established downstream effector pathways(2). However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P-3 (refs 3-5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Forster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss(6,7), required PI(3) K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.",

author = "{van Diepen}, {Michiel T.} and Maddy Parsons and Downes, {C. Peter} and Leslie, {Nicholas R.} and Robert Hindges and Eickholt, {Britta J.}",

year = "2009",

doi = "10.1038/ncb1961",

language = "English",

volume = "11",

pages = "1191 -- 1196",

journal = "Nature Cell Biology",

publisher = "Nature Research",

number = "10",

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TY - JOUR

T1 - MyosinV controls PTEN function and neuronal cell size

AU - van Diepen, Michiel T.

AU - Parsons, Maddy

AU - Downes, C. Peter

AU - Leslie, Nicholas R.

AU - Hindges, Robert

AU - Eickholt, Britta J.

PY - 2009

Y1 - 2009

N2 - The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types(1). PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P-3 to PtdIns(4,5)P-2, thereby antagonizing PI(3) K (phosphoinositide 3-kinase) and its established downstream effector pathways(2). However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P-3 (refs 3-5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Forster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss(6,7), required PI(3) K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

AB - The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types(1). PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P-3 to PtdIns(4,5)P-2, thereby antagonizing PI(3) K (phosphoinositide 3-kinase) and its established downstream effector pathways(2). However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P-3 (refs 3-5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Forster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss(6,7), required PI(3) K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

U2 - 10.1038/ncb1961

DO - 10.1038/ncb1961

M3 - Article

VL - 11

SP - 1191

EP - 1196

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 10

ER -

MyosinV controls PTEN function and neuronal cell size

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