TY - JOUR
T1 - Understanding the distinct subcellular trafficking of CD36 and GLUT4 during the development of myocardial insulin resistance
AU - Luiken, Joost J. F. P.
AU - Nabben, Miranda
AU - Neumann, Dietbert
AU - Glatz, Jan F. C.
N1 - Funding Information:
The authors are greatly indebted to Drs. Robert Schwenk, Laura Steinbusch and Yilin Liu for their pioneering studies on CD36 and GLUT4 traffic in our laboratory, which together have led to the concepts outlined in this review. MN is supported by the Dutch Heart Foundation , Dekker grant # 2019T041 .
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - CD36 and GLUT4 are the main cardiac trans-sarcolemmal transporters for long-chain fatty acids and glucose, respectively. Together they secure the majority of cardiac energy demands. Moreover, these transporters each represent key governing kinetic steps in cardiac fatty acid and glucose fluxes, thereby offering major sites of regulation. The underlying mechanism of this regulation involves a perpetual vesicle-mediated trafficking (recycling) of both transporters between intracellular stores (endosomes) and the cell surface. In the healthy heart, CD36 and GLUT4 translocation to the cell surface is under short-term control of the same physiological stimuli, most notably increased contraction and insulin secretion. However, under chronic lipid overload, a condition that accompanies a Western lifestyle, CD36 and GLUT4 recycling are affected distinctly, with CD36 being expelled to the sarcolemma while GLUT4 is imprisoned within the endosomes. Moreover, the increased CD36 translocation towards the cell surface is a key early step, setting the heart on a route towards insulin resistance and subsequent contractile dysfunction. Therefore, the proteins making up the trafficking machinery of CD36 need to be identified with special focus to the differences with the protein composition of the GLUT4 trafficking machinery. These proteins that are uniquely dedicated to either CD36 or GLUT4 traffic may offer targets to rectify aberrant substrate uptake seen in the lipid-overloaded heart. Specifically, CD36-dedicated trafficking regulators should be inhibited, whereas such GLUT4-dedicated proteins would need to be activated. Recent advances in the identification of CD36-dedicated trafficking proteins have disclosed the involvement of vacuola-rtype H+-ATPase and of specific vesicle-associated membrane proteins (VAMPs). In this review, we summarize these recent findings and sketch a roadmap of CD36 and GLUT4 trafficking compatible with experimental findings.
AB - CD36 and GLUT4 are the main cardiac trans-sarcolemmal transporters for long-chain fatty acids and glucose, respectively. Together they secure the majority of cardiac energy demands. Moreover, these transporters each represent key governing kinetic steps in cardiac fatty acid and glucose fluxes, thereby offering major sites of regulation. The underlying mechanism of this regulation involves a perpetual vesicle-mediated trafficking (recycling) of both transporters between intracellular stores (endosomes) and the cell surface. In the healthy heart, CD36 and GLUT4 translocation to the cell surface is under short-term control of the same physiological stimuli, most notably increased contraction and insulin secretion. However, under chronic lipid overload, a condition that accompanies a Western lifestyle, CD36 and GLUT4 recycling are affected distinctly, with CD36 being expelled to the sarcolemma while GLUT4 is imprisoned within the endosomes. Moreover, the increased CD36 translocation towards the cell surface is a key early step, setting the heart on a route towards insulin resistance and subsequent contractile dysfunction. Therefore, the proteins making up the trafficking machinery of CD36 need to be identified with special focus to the differences with the protein composition of the GLUT4 trafficking machinery. These proteins that are uniquely dedicated to either CD36 or GLUT4 traffic may offer targets to rectify aberrant substrate uptake seen in the lipid-overloaded heart. Specifically, CD36-dedicated trafficking regulators should be inhibited, whereas such GLUT4-dedicated proteins would need to be activated. Recent advances in the identification of CD36-dedicated trafficking proteins have disclosed the involvement of vacuola-rtype H+-ATPase and of specific vesicle-associated membrane proteins (VAMPs). In this review, we summarize these recent findings and sketch a roadmap of CD36 and GLUT4 trafficking compatible with experimental findings.
KW - CD36
KW - GLUT4
KW - Translocation
KW - Endosomes
KW - Vacuolar-type H+-ATPase
KW - Vesicle-associated membrane proteins
KW - Lipid-induced insulin resistance
KW - Cardiomyocytes
KW - FATTY-ACID UPTAKE
KW - TRANSPORTER-CONTAINING VESICLES
KW - STIMULATED GLUCOSE-TRANSPORT
KW - ACTIVATED PROTEIN-KINASE
KW - H+-ATPASE
KW - SKELETAL-MUSCLE
KW - PLASMA-MEMBRANE
KW - CONTRACTILE DYSFUNCTION
KW - TRANSLOCASE (FAT)/CD36
KW - SNARE PROTEINS
U2 - 10.1016/j.bbadis.2020.165775
DO - 10.1016/j.bbadis.2020.165775
M3 - (Systematic) Review article
C2 - 32209364
SN - 0925-4439
VL - 1866
JO - Biochimica et Biophysica Acta-Molecular Basis of Disease
JF - Biochimica et Biophysica Acta-Molecular Basis of Disease
IS - 7
M1 - 165775
ER -