Germinal center-specific protein human germinal center associated lymphoma directly interacts with both myosin and actin and increases the binding of myosin to actin

Authors

  • Xiaoqing Lu,

    1.  Division of Oncology–Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, FL, USA
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    • These authors contributed equally to this work;

  • Katarzyna Kazmierczak,

    1.  Department of Molecular and Cellular Pharmacology, University of Miami, FL, USA
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    • These authors contributed equally to this work;

  • Xiaoyu Jiang,

    1.  Division of Oncology–Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, FL, USA
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    • These authors contributed equally to this work;

  • Michelle Jones,

    1.  Department of Molecular and Cellular Pharmacology, University of Miami, FL, USA
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  • James Watt,

    1.  Department of Physiology and Biophysics, Boston University School of Medicine, MA, USA
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  • David M. Helfman,

    1.  Department of Biological Sciences and Graduate School of Nanoscience and Technology (WCU), Korean Advanced Institute of Science and Technology, Daejon, Korea
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  • Jeffrey R. Moore,

    1.  Department of Physiology and Biophysics, Boston University School of Medicine, MA, USA
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  • Danuta Szczesna-Cordary,

    1.  Department of Molecular and Cellular Pharmacology, University of Miami, FL, USA
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    • These authors contributed equally to this work

  • Izidore S. Lossos

    1.  Division of Oncology–Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, FL, USA
    2.  Department of Molecular and Cellular Pharmacology, University of Miami, FL, USA
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    • These authors contributed equally to this work


I. S. Lossos, MD, Sylvester Comprehensive Cancer Center, Department of Medicine, Division of Hematology–Oncology, University of Miami, 1475 NW 12th Avenue (D8-4), Miami, FL 33136, USA
Fax: +1 305 243 4787
Tel: +1 305 243 4785
E-mail: ilossos@med.miami.edu

Abstract

Human germinal center associated lymphoma (HGAL) is a germinal center-specific gene whose expression correlates with a favorable prognosis in patients with diffuse large B-cell and classic Hodgkin lymphomas. HGAL is involved in negative regulation of lymphocyte motility. The movement of lymphocytes is directly driven by actin polymerization and actin–myosin interactions. We demonstrate that HGAL interacts directly and independently with both actin and myosin and delineate the HGAL and myosin domains responsible for the interaction. Furthermore, we show that HGAL increases the binding of myosin to F-actin and inhibits the ability of myosin to translocate actin by reducing the maximal velocity of myosin head/actin movement. No effects of HGAL on actomyosin ATPase activity and the rate of actin polymerization from G-actin to F-actin were observed. These findings reveal a new mechanism underlying the inhibitory effects of germinal center-specific HGAL protein on lymphocyte and lymphoma cell motility.

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