Research ArticlePain

CDK5 inhibits the clathrin-dependent internalization of TRPV1 by phosphorylating the clathrin adaptor protein AP2μ2

See allHide authors and affiliations

Science Signaling  11 Jun 2019:
Vol. 12, Issue 585, eaaw2040
DOI: 10.1126/scisignal.aaw2040

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Constitutive internalization of a nociceptor

The nonselective cation channel TRPV1 elicits the sensation of burning pain in response to thermal or chemical stimuli and contributes to inflammatory thermal hyperalgesia, the increased sensitivity of inflamed tissues to heat. Liu et al. found that TRPV1 was constitutively internalized in cultured human cells and rat neurons through clathrin-mediated endocytosis. TRPV1 internalization depended on binding to the clathrin adaptor protein complex 2 subunit μ2 (AP2μ2) and was antagonized by phosphorylation of AP2μ2 by cyclin-dependent kinase 5 (CDK5). Treating rats with a peptide that interfered with Cdk5-mediated AP2μ2 phosphorylation reduced inflammatory thermal hyperalgesia, suggesting that strategies for promoting TRPV1 internalization might lead to effective treatments for pain.