Recover Password  New User
Undergraduate Research Project Management System

COMMD1 Action in Hepatocelllular Copper Export

Status Current
Seeking Researchers No
Start Date 11/01/2010
End Date 06/30/2011
Funding Source Alaska Heart Institute
Funding Amount 4,100
Community Partner
Related Course
Last Updated 03/01/2011 11:01PM
Keywords copper, ATP7B, COMMD1

People

Faculty
  Jason Burkhead

Student Researchers
  Jessica Schwartz

Abstract

Copper (Cu) containing enzymes (cuproenzymes) are crucial to normal cellular function and development. The intracellular Cu level is highly regulated and maintained at very low levels. The main route of Cu excretion in mammals is by hepatocytes, the primary functional cells of the liver. The apical membranes of these cells line the biliary canal. All Cu excretion by hepatocytes is mediated by the integral membrane ATPase ATP7B. Under normal physiological conditions, ATP7B resides at the transGolgi network (TGN) where Cu is incorporated into the ferroxidase ceruloplasmin. When the Cu level is elevated, ATP7B transports Cu into membrane compartments and traffics with Cu-containing vesicles to the apical membrane where Cu is released. Immediately following Cu excretion, ATP7B is endocytotically retrieved from the apical membrane. When the Cu level normalizes, ATP7B traffics back to the TGN. The membrane compartments ATP7B is associated with following retrieval from the apical membrane have not been characterized. During this study we will establish the location of ATP7B under elevated Cu conditions.
The components that regulate ATP7B trafficking are also unknown. COMMD1 is a small soluble protein thought to influence ATP7B trafficking. Results consistent with this hypothesis are that when COMMD1 expression is reduced 1) ATP7B fails to return to TGN, 2) ATP7B expression is also reduced, and 3) Cu accumulation occurs. However, the regulatory role of COMMD1 is uncharacterized. COMMD1 may regulate ATP7B trafficking by binding to ATP7B at the endosomal membrane. These proteins have been shown to interact at the N-terminal domain of ATP7B and both COMMD1 and ATP7B co-localize with the endosomal pathway. The regulatory function of COMMD1 on ATP7B trafficking and the point at which this regulation occurs has not been revealed. We will isolate the membrane compartments associated with ATP7B and/or COMMD1 and determine the effect COMMD1 expression has on ATP7B localization.

Shared Project Files (e.g. papers, presentations)

File name Description Uploaded by