Function of SSA subfamily of Hsp70 within and across species varies widely in complementing Saccharomyces cerevisiae cell growth and prion propagation.
BACKGROUND
The cytosol of most eukaryotic cells contains multiple highly conserved Hsp70 orthologs that differ mainly by their spatio-temporal expression patterns. Hsp70s play essential roles in protein folding, transport or degradation, and are major players of cellular quality control processes. However, while several reports suggest that specialized functions of Hsp70 orthologs were selected through evolution, few studies addressed systematically this issue.


RESULTS
We compared the ability of Ssa1p-Ssa4p from Saccharomyces cerevisiae and Ssa5p-Ssa8p from the evolutionary distant yeast Yarrowia lipolytica to perform Hsp70-dependent tasks when expressed as the sole Hsp70 for S. cerevisiae in vivo. We show that Hsp70 isoforms (i) supported yeast viability yet with markedly different growth rates, (ii) influenced the propagation and stability of the [PSI(+)] and [URE3] prions, but iii) did not significantly affect the proteasomal degradation rate of CFTR. Additionally, we show that individual Hsp70 orthologs did not induce the formation of different prion strains, but rather influenced the aggregation properties of Sup35 in vivo. Finally, we show that [URE3] curing by the overexpression of Ydj1p is Hsp70-isoform dependent.


CONCLUSIONS
Despite very high homology and overlapping functions, the different Hsp70 orthologs have evolved to possess distinct activities that are required to cope with different types of substrates or stress situations. Yeast prions provide a very sensitive model to uncover this functional specialization and to explore the intricate network of chaperone/co-chaperone/substrates interactions.
Sharma
Deepak
D
Laboratory of Biochemistry and Genetics, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Martineau
Céline N
CN
Le Dall
Marie-Thérèse
MT
Reidy
Michael
M
Masison
Daniel C
DC
Kabani
Mehdi
M
D001704:Biopolymers; D002455:Cell Division; D005656:Fungal Proteins / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D011328:Prions; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D013045:Species Specificity; D025062:Yarrowia / Q000502:physiology*
D001704:Biopolymers; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D011328:Prions
Nature. 2004 Mar 18;428(6980):319-23
15029195
Genetics. 2009 Jan;181(1):129-37
19015537
J Clin Invest. 1995 Apr;95(4):1854-60
7706492
Curr Alzheimer Res. 2008 Jun;5(3):251-9
18537542
Curr Opin Struct Biol. 2008 Feb;18(1):52-9
18243685
Mol Cell Biol. 2002 Jun;22(11):3590-8
11997496
Proc Natl Acad Sci U S A. 1985 Oct;82(19):6455-9
3931075
Science. 2000 Jul 28;289(5479):595-9
10915616
EMBO J. 1994 Dec 15;13(24):6076-86
7529176
Science. 1989 Sep 8;245(4922):1066-73
2475911
EMBO J. 2001 May 15;20(10):2435-42
11350932
Protein Pept Lett. 2009;16(6):623-60
19519520
Mol Biol Cell. 2007 Jun;18(6):2149-54
17392510
Science. 1996 Jun 14;272(5268):1606-14
8658133
Curr Microbiol. 2001 Jul;43(1):7-10
11375656
Curr Genomics. 2008;9(5):338-248
19471609
EMBO J. 1984 Dec 20;3(13):3095-100
6441707
J Biol Chem. 2003 Dec 5;278(49):49636-43
14507919
Annu Rev Genet. 1988;22:631-77
2853609
Genetics. 2007 Nov;177(3):1679-89
17947402
Genetics. 1994 Jul;137(3):671-6
8088512
EMBO J. 2005 Sep 7;24(17):3082-92
16096644
Cell Mol Life Sci. 2005 Mar;62(6):670-84
15770419
EMBO J. 1992 Oct;11(10):3507-12
1396553
J Mol Biol. 2007 Jan 19;365(3):773-82
17097676
Biochim Biophys Acta. 2007 Jun;1772(6):681-91
17254754
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2339-42
8637874
Curr Biol. 1994 Dec 1;4(12):1104-14
7704574
Mol Microbiol. 2001 Jan;39(1):37-46
11123686
Mol Biol Cell. 2001 May;12(5):1303-14
11359923
Methods Enzymol. 2006;412:33-48
17046650
Methods Mol Med. 2002;70:257-65
11917528
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9936-41
12105276
Cell Stress Chaperones. 2009 Jan;14(1):105-11
18663603
Science. 2001 May 25;292(5521):1552-5
11375494
Mol Microbiol. 2007 Mar;63(6):1669-83
17367387
Science. 1994 Apr 22;264(5158):566-9
7909170
Methods Enzymol. 2006;412:185-200
17046659
Cell. 1998 Jul 10;94(1):73-82
9674429
Nucleic Acids Res. 1995 Mar 11;23(5):883-4
7708509
FEBS Lett. 2007 Jul 31;581(19):3702-10
17544402
PLoS One. 2008 Mar 12;3(3):e1763
18335038
Genetics. 1994 Jul;137(3):659-70
8088511
EMBO J. 2002 Jan 15;21(1-2):12-21
11782421
EMBO Rep. 2000 Sep;1(3):225-31
11256604
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2036-40
1549562
Mol Cell Biol. 2001 Oct;21(20):7035-46
11564886
Genetics. 2003 Feb;163(2):495-506
12618389
Yeast. 1997 Sep 15;13(11):1009-20
9290205
Cancer Res. 1982 Jun;42(6):2457-61
7074623
Nat Rev Microbiol. 2007 Aug;5(8):611-8
17632572
J Histochem Cytochem. 2003 Apr;51(4):545-8
12642634
Biochem J. 2004 Oct 1;383(Pt 1):139-47
15222878
Genetics. 2006 May;173(1):35-47
16452152
Mol Cell Biol. 2000 Dec;20(23):8916-22
11073991
J Biol Chem. 1994 Oct 14;269(41):25710-8
7523390
Nature. 2004 Mar 18;428(6980):323-8
15029196
Eukaryot Cell. 2005 Feb;4(2):289-97
15701791
Genetics. 2008 Jul;179(3):1301-11
18562668
Science. 1995 Oct 6;270(5233):93-5
7569955
Prion. 2007 Oct-Dec;1(4):217-22
19164915
Nature. 2007 Sep 13;449(7159):233-7
17767153
Genetics. 2007 Nov;177(3):1583-93
18039878
J Biol Chem. 1992 Jan 25;267(3):1932-7
1309803
Yeast. 2004 Jan 30;21(2):107-17
14755636
FEMS Yeast Res. 2007 Jan;7(1):110-7
17311589
Genetics. 2000 Oct;156(2):559-70
11014806
Nature. 1994 Dec 1;372(6505):475-8
7984243
J Mol Biol. 1995 May 26;249(1):126-37
7776367
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1681-5
1705702
Science. 1996 Aug 2;273(5275):622-6
8662547
Cell. 1997 May 30;89(5):811-9
9182769
Science. 1995 May 12;268(5212):880-4
7754373
Genetics. 2006 Feb;172(2):851-61
16299395
J Mol Evol. 1994 Jan;38(1):1-17
8151709
Mol Cell Biol. 1987 Jul;7(7):2568-77
3302682
Science. 1994 Feb 18;263(5149):971-3
8310296
EMBO J. 2006 Feb 22;25(4):822-33
16467849