| First Author | Silver DL | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 31 | Pages | 28528-32 |
| PubMed ID | 12754212 | Mgi Jnum | J:97227 |
| Mgi Id | MGI:3574778 | Doi | 10.1074/jbc.M304109200 |
| Citation | Silver DL, et al. (2003) Identification of small PDZK1-associated protein, DD96/MAP17, as a regulator of PDZK1 and plasma high density lipoprotein levels. J Biol Chem 278(31):28528-32 |
| abstractText | 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 (SPAP; also known as DD96/MAP17). Unexpectedly, we found that hepatic overexpression of SPAP in mice resulted in liver deficiency of PDZK1. The absence of PDZK1 in SPAP 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 SPAP overexpression in liver increased PDZK1 turnover in an alternate, proteasome-independent pathway. Thus, SPAP may be an endogenous regulator of cellular PDZK1 levels by regulating PDZK1 turnover. |
