NECABs: A family of neuronal Ca2+-binding proteins with an unusual domain structure and a restricted expression pattern

Ca2+-signalling plays a major role in regulating all aspects of neuronal function. Different types of neurons exhibit characteristic differences in the responses to Ca2+-signals. Correlating with differences in Ca2+-response are expression patterns of Ca2+-binding proteins that often serve as markers for various types of neurons. For example, in the cerebral cortex the EF-hand Ca2+-binding proteins parvalbumin and calbindin are primarily expressed in inhibitory interneurons where they influence Ca2+-dependent responses. We have now identified a new family of proteins called NECABs (neuronal Ca2+-binding proteins). NECABs contain an N-terminal EF-hand domain that binds Ca2+, but different from many other neuronal EF-hand Ca2+-binding proteins, only a single EF-hand domain is present. At the C-terminus, NECABs include a DUF176 motif, a bacterial domain of unknown function that was previously not observed in eukaryotes. In rat at least three closely related NECAB genes are expressed either primarily in brain (NECABs 1 and 2) or in brain and muscle (NECAB 3). Immunocytochemistry revealed that NECAB I is restricted to subsets of neurons. In cerebral cortex, NECAB I is highly and uniformly expressed only in layer 4 pyramidal neurons, whereas in hippocampus only inhibitory interneurons and CA2 pyramidal cells contain NECAB 1. In these neurons, NECAB I fills the entire cytoplasm similar to other EF-hand Ca2+-binding proteins, and is not concentrated in any particular subcellular compartment. We suggest that NECABs represent a novel family of regulatory Ca2+-binding proteins with an unusual domain structure and a limited expression in a subclass of neurons. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.