Schwaller, Beat 2014 The hexa-EF-hand Ca²⁺-binding protein calretinin (CR) is predominantly expressed in specific neurons of the central and peripheral nervous system. However, CR expression is also observed in non-neuronal cells, e.g., during embryonic development and in mesothelioma cells. Of the 6 EF-hand domains, 5 are functional; the first 4 domains form 2 pairs showing high cooperativity within a pair that results in non-linear modulation of intracellular Ca²⁺ signals by CR. EF-hand domain 5 has a low affinity and represents the identified interaction site with CR-binding partners present in mouse cerebellar granule cells. CR binding to other targets including the pore-forming α₁ subunit of the Ca²⁺ channel Ca_<i>V</i>2.1, as well as to huntingtin indicates additional Ca²⁺ sensor functions besides the well-known Ca²⁺-buffering functions. The absence of CR in cerebellar granule cells of CR^−/− mice results in increased excitability and altered firing of Purkinje cells and promotes cerebellar 160-Hz oscillations impairing motor coordination. The putative role of CR in neuroprotection is still highly discussed. Altogether, CR emerges as a multi-functional protein also associated with development, i.e., cell proliferation, differentiation, and cell death. application/pdf https://folia.unifr.ch/global/documents/303405 https://folia.unifr.ch/documents/303405/files/sch_cfs.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.3389/fnana.2014.00003 info:eu-repo/semantics/openAccess License undefined Frontiers in Neuroanatomy. - 2013, vol. 8, p. 3 info:eu-repo/classification/udc/57 Calretinin: from a ‘simple’ Ca2+ buffer to a multifunctional protein implicated in many biological processes http://purl.org/coar/resource_type/c_6501