title: Spatial localisation of chaperone distribution in the endoplasmic reticulum of yeast.
abstract: In eukaryotes, the endoplasmic reticulum (ER) serves as the first membrane-enclosed organelle in the secretory pathway, with functions including protein folding, maturation and transport. Molecular chaperones, of the Hsp70 family of proteins, participate in assisting these processes and are essential to cellular function and survival. BiP is a resident Hsp70 chaperone in the ER of Saccharomyces cerevisiae. In this study the authors have created a partial differential equation model to examine how BiP interacts with the membrane-bound co-chaperone Sec63 in translocation, a process in which BiP assists in guiding a nascent protein into the ER lumen. It has been found that when Sec63 participates in translocation through localisation at the membrane, the spatial distribution of BiP is inhomogeneous, with more BiP at the surface. When translocation is inhibited through a disabling of Sec63's membrane tether, the concentration of BiP throughout the ER becomes homogeneous. The computational simulations suggest that Sec63's localisation and the resulting binding to BiP near the membrane surface of the ER enable a heterogeneous distribution of BiP within the ER, and may facilitate BiP's role in translocation. [Includes supplementary material].
authors.affiliation: Department of Computer Science, University of California, Santa Barbara, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Griesemer
authors.forename: C
authors.initials: C
authors.lastname: Young
authors.forename: A
authors.initials: A
authors.lastname: Robinson
authors.forename: L
authors.initials: L
authors.lastname: Petzold
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C060153:KAR2 protein, yeast; D026901:Membrane Transport Proteins; C074215:SEC63 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins