Identification of small PDZK1-associated protein, DD96/MAP17, as a regulator of PDZK1 and plasma high density lipoprotein levels.

Scavenger receptor class B, type I (SR-BI) is the high density lipoprotein (HDL) receptor essential for hepatic uptake of HDL cholesterol. SR-BI was shown to impact plasma HDL levels and be anti-atherogenic. Thus, the ability to regulate hepatic SR-BI may allow for the modulation of plasma HDL cholesterol and progression of atherosclerosis. However, regulation of SR-BI in liver is not well understood. Recently, the PDZ domain containing protein PDZK1 was shown to interact with SR-BI and may serve an essential role in SR-BI cell surface expression. Here we identify an in vivo PDZK1-interacting protein that we named small PDZK1-associated protein also known as DD96/MAP17). Unexpectedly, we found that hepatic overexpression of in mice resulted in liver deficiency of PDZK1. The absence of PDZK1 in duanyu1842P transgenic mice resulted in a deficiency of SR-BI in liver and markedly increased plasma HDL. Metabolic labeling experiments showed that the proteasome plays a role in the turnover of newly synthesized PDZK1, but that duanyu1842P overexpression in liver increased PDZK1 turnover in an alternate, proteasome-independent pathway. Thus, duanyu1842P may be an endogenous regulator of cellular PDZK1 levels by regulating PDZK1 turnover.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}