Swa2, the yeast homolog of mammalian auxilin, is specifically required for the propagation of the prion variant [URE3-1]

Yeast prions require a core set of chaperone proteins including Sis1, Hsp70 and Hsp104 to generate new amyloid templates for stable propagation, yet emerging studies indicate that propagation of some prions requires additional chaperone activities, demonstrating chaperone specificity beyond the common amyloid requirements. To comprehensively assess such prion-specific requirements for the propagation of the [URE3] prion variant [URE3-1], we screened 12 yeast cytosolic J-proteins, and here we report a novel role for the J-protein Swa2/Aux1. Swa2 is the sole yeast homolog of the mammalian protein auxilin, which, like Swa2, functions in vesicle-mediated endocytosis by disassembling the structural lattice formed by the protein clathrin. We found that, in addition to Sis1, [URE3-1] is specifically dependent upon Swa2, but not on any of the 11 other J-proteins. Further, we show that [URE3-1] propagation requires both a functional J-domain and the tetratricopeptide repeat (TPR) domain, but surprisingly does not require Swa2-clathrin binding. Because the J-domain of Swa2 can be replaced with the J-domains of other proteins, our data strongly suggest that prion-chaperone specificity arises from the Swa2 TPR domain and supports a model where Swa2 acts through Hsp70, most likely to provide additional access points for Hsp104 to promote prion template generation.

Title	Swa2, the yeast homolog of mammalian auxilin, is specifically required for the propagation of the prion variant [URE3-1]
Creator	Nguyen, P. P.
	Troisi, E. M.
	Oliver, E. E.
	Rockman, M. E.
	Hines, Justin K.
Publisher	Molecular Microbiology
Academic Department	Chemistry
Division	Natural Sciences
Organization	Lafayette College
Date Issued	September 2015
Date Available	2015-12-01T16:12:57Z
Type	Article
Language	English
Bibliographic Citation	Troisi, E. M., et al. (2015 Sept.) "Swa2, the yeast homolog of mammalian auxilin, is specifically required for the propagation of the prion variant [URE3-1]." Molecular Microbiology 97 (5): 926-941.
Standard Identifier	DOI 10.1111/mmi.13076
Standard Identifier	Handle 10385/2053
Permalink	http://hdl.handle.net/10385/2053
Rights Statement	Creative Commons - Attribution, Non-Commercial, No Derivatives
Rights Holders	Nguyen, P. P.
	Troisi, E. M.
	Oliver, E. E.
	Rockman, M. E.
	Hines, Justin K.