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Journal of Lipid Research, Vol. 50, 2306-2313, November 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Functional interaction of hormone-sensitive lipase and perilipin in lipolysis

Wen-Jun Shen^*,, Shailja Patel^*,, Hideaki Miyoshi, Andrew S. Greenberg^1, and Fredric B. Kraemer^1,*,

^* Division of Endocrinology, Stanford University, Stanford, California 94305
VA Palo Alto Health Care System, Palo Alto, CA 94304
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111

¹ To whom correspondence should be addressed. e-mail: andrew.greenberg{at}tufts.edu or fbk{at}stanford.edu

Adipocyte lipolysis is controlled by complex interactions of lipases, cofactors, and structural proteins associated with lipid droplets. Perilipin (Plin) A is a major droplet-associated protein that functions as a scaffold, both suppressing basal and facilitating cAMP-dependent protein kinase (PKA)-stimulated lipolysis. Plin is required for the translocation of hormone-sensitive lipase (HSL) from the cytosol to lipid droplets upon stimulation. In these studies, we provide direct evidence for a physical interaction of HSL with Plin. By coexpressing HSL with truncation mutations of Plin, we demonstrate using coimmunoprecipitation that HSL can interact with an N-terminal region located between amino acids 141 and 200 of Plin A as well as with a C-terminal region located between amino acids 406 and 480. The N-terminal construct, Plin 1-200, which does not associate with lipid droplets but interacts with HSL, can function as a dominant negative for PKA-stimulated lipolysis. Using confocal microscopy of Plin truncations, we demonstrate that sequences between amino acids 463 and 517 may be important for or participate in lipid targeting. The results suggest the translocation of HSL to the lipid droplet occurs by virtue of Plin localization to the surface of lipid droplets and a physical interaction of HSL occurring with sequences within the N-terminal region of Plin.

Supplementary key words translocation • lipid droplet • adipocyte

Abbreviations: ACS-1, acyl-coenzyme A synthase 1; ATGL, adipose triglyceride lipase; CGI-58, comparative gene identification 58; CHO, Chinese hamster ovary; DAG, diacylglycerol; FATP1, fatty acid transport protein 1; GST, glutathione S-transferase; HSL, hormone-sensitive lipase; PKA, cAMP-dependent protein kinase; Plin, perilipin; TAG, triacylglycerol

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