A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis

Hongmei Ren, Lorenzo Federico, Huiyan Huang, Manjula Sunkara, Tracy Drennan, Michael A. Frohman, Susan S. Smyth, Andrew J. Morris

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Lipins are phosphatidic acid phosphatases with a pivotal role in regulation of triglyceride and glycerophospholipid metabolism. Lipin1 is also an amplifier of PGC-1α, a nuclear coactivator of PPAR-α responsive gene transcription. Lipins do not contain recognized membrane-association domains, but interaction of these enzymes with cellular membranes is necessary for access to their phospholipid substrate. We identified a role for a conserved polybasic amino acid motif in an N-terminal domain previously implicated as a determinant of nuclear localization in selective binding of lipin1β to phosphatidic acid, using blot overlay assays and model bilayer membranes. Studies using lipin1β polybasic motif variants establish that this region is also critical for nuclear import and raise the possibility that nuclear/cytoplasmic shuttling of lipin1β is regulated by PA. We used pharmacological agents and lipin1β polybasic motif mutants to explore the role of PA-mediated membrane association and nuclear localization on lipin1β function in phospholipid metabolism and adipogenic differentiation. We identify a role for the lipin1 polybasic motif as both a lipid binding motif and a primary nuclear localization sequence. These two functions are necessary for full expression of the biological activity of the protein in intracellular lipid metabolism and transcriptional control of adipogenesis.

Original languageEnglish (US)
Pages (from-to)3171-3181
Number of pages11
JournalMolecular Biology of the Cell
Volume21
Issue number18
DOIs
StatePublished - Sep 15 2010

Fingerprint

Adipogenesis
Phosphatidic Acids
Lipid Metabolism
Membranes
Phospholipids
Phosphatidate Phosphatase
Glycerophospholipids
Amino Acid Motifs
Peroxisome Proliferator-Activated Receptors
Cell Nucleus Active Transport
Nuclear Envelope
Triglycerides
Pharmacology
Lipids
Enzymes
Genes
Proteins
lipine

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Ren, H., Federico, L., Huang, H., Sunkara, M., Drennan, T., Frohman, M. A., ... Morris, A. J. (2010). A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis. Molecular Biology of the Cell, 21(18), 3171-3181. https://doi.org/10.1091/mbc.E10-01-0073

A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis. / Ren, Hongmei; Federico, Lorenzo; Huang, Huiyan; Sunkara, Manjula; Drennan, Tracy; Frohman, Michael A.; Smyth, Susan S.; Morris, Andrew J.

In: Molecular Biology of the Cell, Vol. 21, No. 18, 15.09.2010, p. 3171-3181.

Research output: Contribution to journalArticle

Ren, H, Federico, L, Huang, H, Sunkara, M, Drennan, T, Frohman, MA, Smyth, SS & Morris, AJ 2010, 'A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis', Molecular Biology of the Cell, vol. 21, no. 18, pp. 3171-3181. https://doi.org/10.1091/mbc.E10-01-0073
Ren, Hongmei ; Federico, Lorenzo ; Huang, Huiyan ; Sunkara, Manjula ; Drennan, Tracy ; Frohman, Michael A. ; Smyth, Susan S. ; Morris, Andrew J. / A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis. In: Molecular Biology of the Cell. 2010 ; Vol. 21, No. 18. pp. 3171-3181.
@article{b7a20398bdc2443c9b47618ea115c991,
title = "A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis",
abstract = "Lipins are phosphatidic acid phosphatases with a pivotal role in regulation of triglyceride and glycerophospholipid metabolism. Lipin1 is also an amplifier of PGC-1α, a nuclear coactivator of PPAR-α responsive gene transcription. Lipins do not contain recognized membrane-association domains, but interaction of these enzymes with cellular membranes is necessary for access to their phospholipid substrate. We identified a role for a conserved polybasic amino acid motif in an N-terminal domain previously implicated as a determinant of nuclear localization in selective binding of lipin1β to phosphatidic acid, using blot overlay assays and model bilayer membranes. Studies using lipin1β polybasic motif variants establish that this region is also critical for nuclear import and raise the possibility that nuclear/cytoplasmic shuttling of lipin1β is regulated by PA. We used pharmacological agents and lipin1β polybasic motif mutants to explore the role of PA-mediated membrane association and nuclear localization on lipin1β function in phospholipid metabolism and adipogenic differentiation. We identify a role for the lipin1 polybasic motif as both a lipid binding motif and a primary nuclear localization sequence. These two functions are necessary for full expression of the biological activity of the protein in intracellular lipid metabolism and transcriptional control of adipogenesis.",
author = "Hongmei Ren and Lorenzo Federico and Huiyan Huang and Manjula Sunkara and Tracy Drennan and Frohman, {Michael A.} and Smyth, {Susan S.} and Morris, {Andrew J.}",
year = "2010",
month = "9",
day = "15",
doi = "10.1091/mbc.E10-01-0073",
language = "English (US)",
volume = "21",
pages = "3171--3181",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "18",

}

TY - JOUR

T1 - A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis

AU - Ren, Hongmei

AU - Federico, Lorenzo

AU - Huang, Huiyan

AU - Sunkara, Manjula

AU - Drennan, Tracy

AU - Frohman, Michael A.

AU - Smyth, Susan S.

AU - Morris, Andrew J.

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Lipins are phosphatidic acid phosphatases with a pivotal role in regulation of triglyceride and glycerophospholipid metabolism. Lipin1 is also an amplifier of PGC-1α, a nuclear coactivator of PPAR-α responsive gene transcription. Lipins do not contain recognized membrane-association domains, but interaction of these enzymes with cellular membranes is necessary for access to their phospholipid substrate. We identified a role for a conserved polybasic amino acid motif in an N-terminal domain previously implicated as a determinant of nuclear localization in selective binding of lipin1β to phosphatidic acid, using blot overlay assays and model bilayer membranes. Studies using lipin1β polybasic motif variants establish that this region is also critical for nuclear import and raise the possibility that nuclear/cytoplasmic shuttling of lipin1β is regulated by PA. We used pharmacological agents and lipin1β polybasic motif mutants to explore the role of PA-mediated membrane association and nuclear localization on lipin1β function in phospholipid metabolism and adipogenic differentiation. We identify a role for the lipin1 polybasic motif as both a lipid binding motif and a primary nuclear localization sequence. These two functions are necessary for full expression of the biological activity of the protein in intracellular lipid metabolism and transcriptional control of adipogenesis.

AB - Lipins are phosphatidic acid phosphatases with a pivotal role in regulation of triglyceride and glycerophospholipid metabolism. Lipin1 is also an amplifier of PGC-1α, a nuclear coactivator of PPAR-α responsive gene transcription. Lipins do not contain recognized membrane-association domains, but interaction of these enzymes with cellular membranes is necessary for access to their phospholipid substrate. We identified a role for a conserved polybasic amino acid motif in an N-terminal domain previously implicated as a determinant of nuclear localization in selective binding of lipin1β to phosphatidic acid, using blot overlay assays and model bilayer membranes. Studies using lipin1β polybasic motif variants establish that this region is also critical for nuclear import and raise the possibility that nuclear/cytoplasmic shuttling of lipin1β is regulated by PA. We used pharmacological agents and lipin1β polybasic motif mutants to explore the role of PA-mediated membrane association and nuclear localization on lipin1β function in phospholipid metabolism and adipogenic differentiation. We identify a role for the lipin1 polybasic motif as both a lipid binding motif and a primary nuclear localization sequence. These two functions are necessary for full expression of the biological activity of the protein in intracellular lipid metabolism and transcriptional control of adipogenesis.

UR - http://www.scopus.com/inward/record.url?scp=77956703908&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956703908&partnerID=8YFLogxK

U2 - 10.1091/mbc.E10-01-0073

DO - 10.1091/mbc.E10-01-0073

M3 - Article

C2 - 20660155

AN - SCOPUS:77956703908

VL - 21

SP - 3171

EP - 3181

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 18

ER -