Abstract: Series 102, Lecture 3
The Harvey Lectures Series 102 (2006—2007)
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Lecture #3: Thursday, January 18, 2007 — Time and Location
Transport of Proteins In and Out of the Endoplasmic Reticulum
Tom A Rapoport, PhD
Professor, Department Cell Biology
Investigator, Howard Hughes Medical Institute
Howard Hughes Medical Institute, Harvard Medical School
Boston, Massachusetts
Many proteins are transported during their biosynthesis across or are integrated into the endoplasmic reticulum (ER) membrane or the bacterial plasma membrane. Transport occurs through a protein-conducting channel, formed from a conserved heterotrimeric membrane protein complex (Sec61/ SecYcomplex). The channel associates with different partners in different translocation pathways. The crystal structure of an archaeal SecY complex suggests mechanisms for how the membrane barrier for small molecules can be maintained during translocation, how the signal sequence is recognized, and how trans-membrane segments of nascent membrane proteins exit into lipid.
In eukarotes, there is a much less understood translocation pathway in the reverse direction, called ERAD (for ER-associated degradation), by which misfolded ER proteins are transported back into the cytosol where they are poly-ubiquitinated and degraded by the proteasome. Different, but convergent, ERAD pathways are used for proteins with misfolded domains in the lumen, membrane, or cytosol (called ERAD-L, -M, and –C, respectively). The recent identification of most, if not all, components of the ERAD pathways paves the way for a mechanistic understanding of retro-translocation.