title: Molecular interactions between presenilin and calpain: inhibition of m-calpain protease activity by presenilin-1, 2 and cleavage of presenilin-1 by m-, mu-calpain.
abstract: Several mutations of presenilin (PS)-1, 2 result in early onset Alzheimer disease. Using the yeast two-hybrid system, the interaction between PS2 loop domain and the C-terminal region of mu-calpain was previously identified. Calpain is a calcium dependent-protease and there are two isoforms, m-calpain and mu-calpain, which differ in the calcium concentration required for activation. m-Calpain needs about 10(-3) M calcium ions, whereas mu-calpain about 10(-5) M. When PS and calpain were separately expressed in COS cells by cDNA transfection and then combined in vitro, or both were co-transfected to be co-expressed in vivo in COS cells, PS1 and PS2 reduced the casein proteolysis activity of m-calpain but not that of mu-calpain. Some of the PS mutations related to Alzheimer disease decreased this inhibitory activity. On the other hand, PS1 was cleaved by m-calpain and mu-calpain at a different site from those already reported (constitutive cleavage or alternative cleavage). These results suggest a regulatory function of presenilin on the calpain system.
authors.affiliation: Department of Molecular Biology, Tokyo Institute of Psychiatry, Kamikitazawa, Setagaya, Tokyo 156-8585, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: M
authors.initials: M
authors.lastname: Usami
authors.forename: F
authors.initials: F
authors.lastname: Kametani
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: T C
authors.initials: TC
authors.lastname: Saido
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D000818:Animals; D019556:COS Cells; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D053764:Presenilin-1; D053766:Presenilin-2; D013379:Substrate Specificity
chemical_list: D008565:Membrane Proteins; D053764:Presenilin-1; D053766:Presenilin-2; D002154:Calpain