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J. Biol. Chem., Vol. 282, Issue 48, 35211-35221, November 30, 2007

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Proper Perinuclear Localization of the TRIM-like Protein Myospryn Requires Its Binding Partner Desmin^*

From the Cell Biology Division, Center of Basic Research, Biomedical Research Foundation Academy of Athens, Athens 11527, Greece

Desmin, the muscle-specific intermediate filament protein, surrounds the Z disks and links the entire contractile apparatus to the sarcolemmal cytoskeleton, cytoplasmic organelles, and the nucleus. In an attempt to explore the molecular mechanisms of these associations, we performed a yeast two-hybrid screening of a cardiac cDNA library. We showed that the desmin amino-terminal domain (N-(1-103)) binds to a 413-kDa TRIM-like protein, myospryn, originally identified as the muscle-specific partner of dysbindin, a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Binding of desmin with myospryn was confirmed with glutathione S-transferase pulldown assays and coimmunoprecipitation experiments. Western blot analysis revealed that the complex immunoprecipitated by desmin antibodies, in addition to myospryn, contained the BLOC-1 components dysbindin and pallidin. Deletion analysis revealed that only the (N-(1-103)) fragment of desmin binds to myospryn carboxyl terminus and that this association takes place through the 24-amino acid-long carboxyl-terminal end of the SPRY domain of myospryn. Using an antibody against the COOH terminus of myospryn, we demonstrated that myospryn colocalizes with desmin at the periphery of the nucleus, in close proximity to the endoplasmic reticulum, of mouse neonatal cardiomyocytes. In adult heart muscle, the two proteins colocalize, predominantly at intercalated disks and costameres. We also showed that myospryn colocalizes with lysosomes. Using desmin null hearts, we determined that desmin is required for both the proper perinuclear localization of myospryn, as well as the proper positioning of lysosomes, thus suggesting a potential role of desmin intermediate filaments in lysosomes and lysosome-related organelle biogenesis and/or positioning.

Received for publication, June 8, 2007 , and in revised form, September 4, 2007.

^* This work was supported by the Biomedical Research Foundation of the Academy of Athens, by Karatheodoris scholarship grants from the University of Patras Greece, and by EPAN Grant YB22 from the General Secretariat of Research and Development, Ministry of Development of Greece. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-3.

¹ To whom correspondence should be addressed: Cell Biology Division, Center of Basic Research, Biomedical Research Foundation Academy of Athens, Soranou Efesiou 4, Athens 11527, Greece. Tel.: 30-210-6597212; Fax: 30-210-6597545; E-mail: ycapetanaki{at}bioacademy.gr or yassemic{at}bcm.tmc.edu.

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