Reactome | GFAP binds LAMP2a multimer

GFAP binds LAMP2a multimer

Stable Identifier

R-HSA-9625197

Type

Reaction [binding]

Species

Homo sapiens

Compartment

lysosomal lumen, lysosomal membrane

ReviewStatus

5/5

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Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds KFERQ-domain containing substrates in the cytosol. Consequently, the HSPA8:Substrate complex translocates from cytosol to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, HSPA8 is released and Heat shock protein HSP 90 binds to the lysosomal luminal end of LAMP2a. This LAMP2a complex then multimerizes into a 700 kDa entity and is stabilized by the binding of Glial fibrillary acidic protein (GFAP) (Bandyopadhyay U et al. 2010). Subsequently, the substrate is unfolded and internalized into the lumen. Experiments confirming this binding were performed on rat models.

Literature References

PubMed ID	Title	Journal	Year
20797626	Identification of regulators of chaperone-mediated autophagy Bandyopadhyay, U, Sridhar, S, Kaushik, S, Kiffin, R, Cuervo, AM	Mol. Cell	2010
21282471	Chaperone-mediated autophagy at a glance Kaushik, S, Bandyopadhyay, U, Sridhar, S, Kiffin, R, Martinez-Vicente, M, Kon, M, Orenstein, SJ, Wong, E, Cuervo, AM	J. Cell. Sci.	2011