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Chaperone mediated autophagy (CMA) is a selective autophagy pathway whereby cytosolic proteins bearing a recognition motif are individually recognized and translocated into the lysosomal lumen for degradation. The KFERQ motif s recognized by the Hsc70 chaperone Hspa8, a chaperone/co-chaperone complex targets the substrate to the lysosomal membrane where it interacts with the cytosolic tail of single-span membrane protein Lamp2a. Lamp2a multimerization and formation of a 700kDa complex promotes

Pathway Diagram:

Elsevier Inc. CMA targets cathepsins LysHspa8 Lamp2a multimer Bag1 ---> ATP ADP ---> ATP Hsp8a factors ADP-bound Hspa8 state ATP-bound Hspa8 state Gfap dissoc ---- P-Gfap Eef1a1 Gfap Lamp2a dissoc KFERQ motif ---- Lamp2 Eef1a1 ---- P-Gfap Bag1 Hspa8 ---- KFERQ motif Gfap ---- Lamp2a multimer Dnajb1 Hsp8a factors ---- Hspa8 ATP ---- Hspa8 ATP ADP ---- Hspa8 ADP Dnajb1 ---> ADP ATP ---> ADP Hspa8 Lamp2 KFERQ motif ---> KFERQ translocated CMA target degradation cathepsins ---> CMA targets KFERQ motif KFERQ translocated Gfap dissoc P-Gfap

Genes in Pathway:

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chaperone mediated autophagy pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Bag1 Bcl2 associated athanogene 1 JBrowse link 5 57,254,421 57,267,002 RGD:10755685
G Ctsb cathepsin B JBrowse link 15 46,316,741 46,337,613 RGD:10755730
G Ctsd cathepsin D JBrowse link 1 215,541,570 215,553,446 RGD:10755729
G Ctsl cathepsin L JBrowse link 17 1,873,105 1,879,266 RGD:10755730
G Dnajb1 DnaJ heat shock protein family (Hsp40) member B1 JBrowse link 19 24,747,178 24,750,919 RGD:10755685
G Eef1a1 eukaryotic translation elongation factor 1 alpha 1 JBrowse link 8 85,838,594 85,841,816 RGD:10755322
G Gfap glial fibrillary acidic protein JBrowse link 10 90,990,762 90,999,435 RGD:10755322
G Hsp90aa1 heat shock protein 90 alpha family class A member 1 JBrowse link 6 135,107,262 135,112,793 RGD:10755685
G Hspa8 heat shock protein family A (Hsp70) member 8 JBrowse link 8 44,989,401 44,993,261 RGD:10755322
G Lamp2 lysosomal-associated membrane protein 2 JBrowse link X 124,722,628 124,766,079 RGD:10755322
G St13 ST13, Hsp70 interacting protein JBrowse link 7 122,585,770 122,635,731 RGD:10755685
G Stip1 stress-induced phosphoprotein 1 JBrowse link 1 222,274,133 222,293,139 RGD:10755685

Pathway Gene Annotations

Pathway Annotations Associated with Genes in the chaperone mediated autophagy pathway
Pathway TermsGene Symbols
aldosterone signaling pathwayHsp90aa1
androgen signaling pathwayHsp90aa1 , Hspa8 , St13 , Stip1
antigen processing and presentation pathwayCtsb , Ctsl , Hsp90aa1 , Hspa8
autophagy pathwayLamp2
ceramide signaling pathwayCtsd
chaperone mediated autophagy pathwayBag1 , Ctsb , Ctsd , Ctsl , Dnajb1 , Eef1a1 , Gfap , Hsp90aa1 , Hspa8 , Lamp2 , St13 , Stip1
clathrin-dependent synaptic vesicle endocytosisHspa8
cortisol signaling pathwayHsp90aa1 , Stip1
endocytosis pathwayHspa8
Endoplasmic Reticulum-associated degradation pathwayBag1 , Dnajb1 , Hsp90aa1 , Hspa8
epidermal growth factor/neuregulin signaling pathwayHsp90aa1
estrogen signaling pathwayHsp90aa1 , Stip1
influenza A virus infection pathwayDnajb1 , Hspa8
measles infection pathwayHspa8
mitogen activated protein kinase signaling pathwayHspa8
Mycobacterium tuberculosis infection pathwayCtsd , Lamp2
NOD-like receptor signaling pathwayHsp90aa1
phagocytosis pathwayCtsl , Lamp2
phosphatidylinositol 3-kinase class I signaling pathwayHsp90aa1
phosphatidylinositol 3-kinase-Akt signaling pathwayHsp90aa1
prednisolone pharmacodynamics pathwayHsp90aa1
prednisolone pharmacokinetics pathwayHsp90aa1
prion diseases pathwayStip1
prostate cancer pathwayHsp90aa1
protein kinase C (PKC) signaling pathwayHsp90aa1
rheumatoid arthritis disease pathwayCtsl
RNA transport pathwayEef1a1
spliceosome pathwayHspa8
Toxoplasma gondii infection pathwayHspa8
translation elongation pathwayEef1a1
vascular endothelial growth factor signaling pathwayHsp90aa1

References Associated with the chaperone mediated autophagy pathway:

Ontology Path Diagram:

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