The molecular and functional interaction between ICLN and HSPCo38 modulates the regulation of cell volume
2011 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 47, 40659-40670 p.Article in journal (Refereed) Published
Identifying functional partners for protein/protein interactions can be a difficult challenge. We proposed the use of the operon structure of the Caenorhabditis elegans genome as a 'New Gene-Finding Tool' (Eichmueller et al, JBC, 2004, 279:7136) that could be functionally translated to the human system. Here we show the validity of this approach by studying the predicted functional interaction between ICln and HSPC038. In Caenorhabditis elegans, the gene encoding for the ICln homolog (icln-1) is embedded in an operon with two other genes, Nx (the human homolog of Nx is HSPC038) and Ny. ICln is a highly conserved, ubiquitously expressed multifunctional protein that plays a critical role in the regulatory volume decrease after cell swelling. Following hypotonic stress, ICln translocates from the cytosol to the plasma membrane, where it has been proposed to participate in the activation of the swelling induced chloride current (IClswell). Here we show that the interaction between human ICln and HSPC038 plays a role in volume regulation after cell swelling and that HSPC038 acts as an escort, directing ICln to the cell membrane after cell swelling and facilitating the activation of IClswell. Assessment of the NMR structure of HSPC038 showed the presence of a zinc finger motif. Moreover, NMR and additional biochemical techniques enabled us to identify the putative ICln/HSPC038 interacting sites, thereby explaining the functional interaction of both proteins on a molecular level.
Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2011. Vol. 286, no 47, 40659-40670 p.
choride transport, gene regulation, membrane, protein assembly, protein translocation
IdentifiersURN: urn:nbn:se:umu:diva-47559DOI: 10.1074/jbc.M111.260430PubMedID: 21917931OAI: oai:DiVA.org:umu-47559DiVA: diva2:442977
First Published on September 14, 20112011-09-232011-09-232011-12-30Bibliographically approved