Voelcker Academy
previous next
Helen Smith

Adiponectin Activates AMPK in Muscle Cells Via APPL1/LKB1- and Ca2+/CaMKK-dependent Pathways

Helen Smith

Mentor: Dr. Lily Q. Dong

APPL1, an adaptor protein, needs to bind to adiponectin receptors in order for adiponectin-induced AMPK activation to happen in muscle. However, scientists do not know the underlying molecular mechanism of this process. These experiments show that in muscle cells, adiponectin promotes LKB1 cytosolic translocation to induce AMPK activation. Cytosolic translocation is relocation from the nucleus to the cytosol. APPL1 anchors the LKB1 outside the nucleus after cytosolic translocation. AAPL1 controls adiponectin signaling when it interacts directly with adiponectin receptors and when it anchors LKB1 in the cytosol to enhance this kinase cytosolic localization. Adiponectin activates another AMPK upstream kinase, CaMKK, as well. Adiponectin activates CaMKK by starting Ca2+- release from sources inside the cell. Adiponectin can activate AMPK in two mechanisms, an APPL1/LKB1-dependent path which is activated by controlling the cytosolic localization of LKB1 and a Ca2+/CaMKK-dependent path activated by releasing Ca2+ from cell stores, in muscle cells.

Collaborators: Feng Liu, Deepa Sathyaseelan, Lijun Zhou, Julie C. Etzler, Jiyoon Ryu, Xuming Mao, Dianna D. Liu and James D. Lechleiter