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Vol. 12, Issue 10, 3242-3256, October 2001
Department Clinical Biochemistry, Cambridge Institute for Medical
Research, University of Cambridge, Addenbrookes Hospital, Cambridge,
CB2 2XY, United Kingdom
Endosome-to-Golgi retrieval of the carboxypeptidase Y
receptor Vps10p is mediated by a recently discovered membrane coat
complex termed retromer. Retromer comprises five conserved proteins:
Vps35p, Vps29p, Vps5p, Vps17p, and Vps26p. Vps35p recognizes cargo
molecules such as Vps10p and interacts strongly with Vps29p. Vps5p
forms a subcomplex with Vps17p and has been proposed to play a
structural role by self-assembling into large multimeric structures.
The function of Vps26p is currently unknown. We have investigated the
role that Vps26p plays in retromer-mediated endosome-to-Golgi transport
by analyzing dominant negative alleles of Vps26p. These mutants have
identified a crucial region of Vps26p that plays an important role in
its function. Functional domains of Vps26p have been investigated by
the creation of yeast-mouse hybrid molecules in which domains of Vps26p
have been replaced by the similar domain in the protein encoded by the
mouse VPS26 gene, H
58. These domain swap experiments have shown that
Vps26p promotes the interactions between the cargo-selective component
Vps35p and the structural components Vps5p/Vps17p.
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