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Updated: Mar 9, 2026

Detection of Detergent-sensitive Interactions Between Membrane Proteins
Published on: March 7, 2018
DHHC7 Palmitoylates Glucose Transporter 4 (Glut4) and Regulates Glut4 Membrane Translocation
Keyong Du1, Shoko Murakami2, Yingmin Sun3
1From the Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111 and kdu@tuftsmedicalcenter.org.
Abstract:
Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane plays a key role in the dynamic regulation of glucose homeostasis. We recently showed that this process is critically dependent on palmitoylation of Glut4 at Cys-223. To gain further insights into the regulation of Glut4 palmitoylation, we set out to identify the palmitoyl acyltransferase (PAT) involved. Here we report that among 23 mammalian DHHC proteins, DHHC7 is the major Glut4 PAT, based on evidence that ectopic expression of DHHC7 increased Glut4 palmitoylation, whereas DHHC7 knockdown in 3T3-L1 adipocytes and DHHC7 KO in adipose tissue and muscle decreased Glut4 palmitoylation. Moreover, inactivation of DHHC7 suppressed insulin-dependent Glut4 membrane translocation in both 3T3-L1 adipocytes and primary adipocytes. Finally, DHHC7 KO mice developed hyperglycemia and glucose intolerance, thereby confirming that DHHC7 represents the principal PAT for Glut4 and that this mechanism is essential for insulin-regulated glucose homeostasis.
Related Concept Videos
Membrane Proteins
Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Glucose Absorption Into the Small Intestine
Insulin: The Receptor and Signaling Pathways
Insulin Secretory Vesicles
Secondary Active Transport

