NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathwaysShow others and affiliations
2000 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 19, no 14, p. 3597-3607Article in journal (Refereed) Published
Abstract [en]
Inhibitor-of-apoptosis proteins (IAPs), including neuronal apoptosis inhibitory protein (NAIP), inhibit cell death. Other IAPs inhibit key caspase proteases which effect cell death, but the mechanism by which NAIP acts is unknown. Here we report that NAIP, through its third baculovirus inhibitory repeat domain (BIR3), binds the neuron-restricted calcium-binding protein, hippocalcin, in an interaction promoted by calcium. In neuronal cell lines NSC-34 and Neuro-2a, over-expression of the BIR domains of NAIP (NAIP-BIR1-3) counteracted the calcium-induced cell death induced by ionomycin and thapsigargin. This protective capacity was significantly enhanced when NAIP-BIR1-3 was co-expressed with hippocalcin. Over-expression of the BIR3 domain or hippocalcin alone did not substantially enhance cell survival, but co-expression greatly increased their protective effects. These data suggest synergy between NAIP and hippocalcin in facilitating neuronal survival against calcium-induced death stimuli mediated through the BIR3 domain. Analysis of caspase activity after thapsigargin treatment revealed that caspase-3 is activated in NSC-34, but not Neuro-2a, cells, Thus NAIP, in conjunction with hippocalcin, can protect neurons against calcium-induced cell death in caspase-3-activated and non-activated pathways.
Place, publisher, year, edition, pages
Univ Uppsala, Biomed Ctr, Dept Neurosci, Uppsala, Sweden. Univ Uppsala, Dept Physiol, Div Cellular Physiol, S-75123 Uppsala, Sweden.: Oxford University Press, 2000. Vol. 19, no 14, p. 3597-3607
Keywords [en]
caspase, hippocalcin, IAP, motor neuron, NAIP
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-168008DOI: 10.1093/emboj/19.14.3597ISI: 000088447000009PubMedID: 10899114Scopus ID: 2-s2.0-0034679676OAI: oai:DiVA.org:liu-168008DiVA, id: diva2:1457428
2020-08-112020-08-112023-12-28Bibliographically approved