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  • The EMBO Journal (2006) 25, 2155 - 2166
  • doi:10.1038/sj.emboj.7601097

Published online: 20 April 2006

Interaction of Moloney murine leukemia virus matrix protein with IQGAP

Juliana Leung1, Andrew Yueh2,a, Frank SK Appah Jr1, Bing Yuan1,b, Kenia de los Santos2 and Stephen P Goff1,2

  1. Integrated Program in Cellular, Molecular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY, USA
  2. Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY, USA

Correspondence to:

Stephen P Goff, Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Tel.: +1 212 305 3794; Fax: +1 212 305 5106; E-mail: goff@cancercenter.columbia.edu

aPresent address: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taipei, Taiwan, ROC

bPresent address: Eos LLP, Teaneck, NJ 07666, USA

Received 14 November 2005; Accepted 27 March 2006

The matrix protein (MA) of the Moloney murine leukemia virus (M-MuLV) was found to interact with IQGAP1, a prominent regulator of the cytoskeleton. Mutational studies defined residues of MA critical for the interaction, and tests of viruses carrying MA mutations revealed a near-perfect correlation between binding and virus replication. The replication-defective mutants showed defects in both early and late stages of the life cycle. Four viable second-site revertant viruses were isolated from three different replication-defective parental mutants, and in all cases the interaction with IQGAP1 was restored by the suppressor mutations. The interaction of MA and IQGAP1 was readily detected in vitro and in vivo. Virus replication was potently inhibited by a C-terminal fragment of IQGAP1, and impaired by RNAi knockdown of IQGAP1 and 2. We suggest that the IQGAPs link the virus to the cytoskeleton for trafficking both into and out of the cell.

  • Keywords:

    • cytoskeleton,
    • IQGAP,
    • murine leukemia virus,
    • retrovirus replication,
    • trafficking