ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function.

Nobuko Kawaguchi; Christina Sundberg; Marie Kveiborg; Behzad Moghadaszadeh; Meena Asmar; Nikolaj Dietrich; Charles K Thodeti; Finn C Nielsen; Peter Möller; Arthur M Mercurio; Reidar Albrechtsen; Ulla M. Wewer

doi:10.1242/jcs.00699

ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function.

Nobuko Kawaguchi, Christina Sundberg, Marie Kveiborg, Behzad Moghadaszadeh, Meena Asmar, Nikolaj Dietrich, Charles K Thodeti, Finn C Nielsen, Peter Möller, Arthur M Mercurio, Reidar Albrechtsen, Ulla M. Wewer

Department of Biomedical Sciences

115 Citations (Scopus)

Abstract

Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation.

Original language	English
Journal	Journal of Cell Science
Volume	116
Issue number	Pt 19
Pages (from-to)	3893-904
Number of pages	11
ISSN	0021-9533
DOIs	https://doi.org/10.1242/jcs.00699
Publication status	Published - 2003

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10.1242/jcs.00699

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Kawaguchi, N., Sundberg, C., Kveiborg, M., Moghadaszadeh, B., Asmar, M., Dietrich, N., Thodeti, C. K., Nielsen, F. C., Möller, P., Mercurio, A. M., Albrechtsen, R., & Wewer, U. M. (2003). ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function. Journal of Cell Science, 116(Pt 19), 3893-904. https://doi.org/10.1242/jcs.00699

ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function. / Kawaguchi, Nobuko; Sundberg, Christina; Kveiborg, Marie et al.
In: Journal of Cell Science, Vol. 116, No. Pt 19, 2003, p. 3893-904.

Research output: Contribution to journal › Journal article › Research › peer-review

Kawaguchi, N, Sundberg, C, Kveiborg, M, Moghadaszadeh, B, Asmar, M, Dietrich, N, Thodeti, CK, Nielsen, FC, Möller, P, Mercurio, AM, Albrechtsen, R & Wewer, UM 2003, 'ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function.', Journal of Cell Science, vol. 116, no. Pt 19, pp. 3893-904. https://doi.org/10.1242/jcs.00699

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title = "ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function.",

abstract = "Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation.",

author = "Nobuko Kawaguchi and Christina Sundberg and Marie Kveiborg and Behzad Moghadaszadeh and Meena Asmar and Nikolaj Dietrich and Thodeti, {Charles K} and Nielsen, {Finn C} and Peter M{\"o}ller and Mercurio, {Arthur M} and Reidar Albrechtsen and Wewer, {Ulla M.}",

note = "Keywords: ADAM Proteins; Actins; Adipocytes; Animals; Antigens, CD29; Cell Adhesion; Cell Differentiation; Cell Size; Cells, Cultured; Cloning, Molecular; Cricetinae; Cricetulus; Cytoskeleton; Extracellular Matrix; Fibronectins; Flow Cytometry; Humans; Membrane Proteins; Metalloendopeptidases; Mice; Octoxynol; Protein Binding; RNA, Small Interfering; Retroviridae; Stress Fibers",

year = "2003",

doi = "10.1242/jcs.00699",

language = "English",

volume = "116",

pages = "3893--904",

journal = "Journal of Cell Science",

issn = "0021-9533",

publisher = "The/Company of Biologists Ltd.",

number = "Pt 19",

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TY - JOUR

T1 - ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function.

AU - Kawaguchi, Nobuko

AU - Sundberg, Christina

AU - Kveiborg, Marie

AU - Moghadaszadeh, Behzad

AU - Asmar, Meena

AU - Dietrich, Nikolaj

AU - Thodeti, Charles K

AU - Nielsen, Finn C

AU - Möller, Peter

AU - Mercurio, Arthur M

AU - Albrechtsen, Reidar

AU - Wewer, Ulla M.

N1 - Keywords: ADAM Proteins; Actins; Adipocytes; Animals; Antigens, CD29; Cell Adhesion; Cell Differentiation; Cell Size; Cells, Cultured; Cloning, Molecular; Cricetinae; Cricetulus; Cytoskeleton; Extracellular Matrix; Fibronectins; Flow Cytometry; Humans; Membrane Proteins; Metalloendopeptidases; Mice; Octoxynol; Protein Binding; RNA, Small Interfering; Retroviridae; Stress Fibers

PY - 2003

Y1 - 2003

N2 - Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation.

AB - Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation.

U2 - 10.1242/jcs.00699

DO - 10.1242/jcs.00699

M3 - Journal article

C2 - 12915587

SN - 0021-9533

VL - 116

SP - 3893

EP - 3904

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - Pt 19

ER -

ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function.

Abstract

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