Appl1: Role in adiponectin signaling and beyond

Sathyaseelan S. Deepa, Lily Q Dong

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Adiponectin, an adipokine secreted by the white adipose tissue, plays an important role in regulating glucose and lipid metabolism and controlling energy homeostasis in insulin-sensitive tissues. A decrease in the circulating level of adiponectin has been linked to insulin resistance, type 2 diabetes, atherosclerosis, and metabolic syndrome. Adiponectin exerts its effects through two membrane receptors, AdipoR1 and AdipoR2. APPL1 is the first identified protein that interacts directly with adiponectin receptors. APPL1 is an adaptor protein with multiple functional domains, the Bin1/amphiphysin/rvs167, pleckstrin homology, and phosphotyrosine binding domains. The PTB domain of APPL1 interacts directly with the intracellular region of adiponectin receptors. Through this interaction, APPL1 mediates adiponectin signaling and its effects on metabolism. APPL1 also functions in insulin-signaling pathway and is an important mediator of adiponectin-dependent insulin sensitization in skeletal muscle. Adiponectin signaling through APPL1 is necessary to exert its anti-inflammatory and cytoprotective effects on endothelial cells. APPL1 also acts as a mediator of other signaling pathways by interacting directly with membrane receptors or signaling proteins, thereby playing critical roles in cell proliferation, apoptosis, cell survival, endosomal trafficking, and chromatin remodeling. This review focuses mainly on our current understanding of adiponectin signaling in various tissues, the role of APPL1 in mediating adiponectin signaling, and also its role in the cross-talk between adiponectin/insulin-signaling pathways.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume296
Issue number1
DOIs
StatePublished - Jan 2009

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Adiponectin
Adiponectin Receptors
Insulin
White Adipose Tissue
Phosphotyrosine
Proteins
Adipokines
Chromatin Assembly and Disassembly
Membranes
Lipid Metabolism
Type 2 Diabetes Mellitus
Insulin Resistance
Cell Survival
Atherosclerosis
Skeletal Muscle
Homeostasis
Anti-Inflammatory Agents
Endothelial Cells
Cell Proliferation
Apoptosis

Keywords

  • Adaptor protein containing pleckstrin homology domain
  • And leucine zipper motif
  • Phosphotyrosine binding domain

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Appl1 : Role in adiponectin signaling and beyond. / Deepa, Sathyaseelan S.; Dong, Lily Q.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 296, No. 1, 01.2009.

Research output: Contribution to journalArticle

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