title: NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual domain structure and a restricted expression pattern.
abstract: Ca(2+)-signalling plays a major role in regulating all aspects of neuronal function. Different types of neurons exhibit characteristic differences in the responses to Ca(2+)-signals. Correlating with differences in Ca(2+)-response are expression patterns of Ca(2+)-binding proteins that often serve as markers for various types of neurons. For example, in the cerebral cortex the EF-hand Ca(2+)-binding proteins parvalbumin and calbindin are primarily expressed in inhibitory interneurons where they influence Ca(2+)-dependent responses. We have now identified a new family of proteins called NECABs (neuronal Ca(2+)-binding proteins). NECABs contain an N-terminal EF-hand domain that binds Ca(2+), but different from many other neuronal EF-hand Ca(2+)-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 1 is restricted to subsets of neurons. In cerebral cortex, NECAB 1 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 1 fills the entire cytoplasm similar to other EF-hand Ca(2+)-binding proteins, and is not concentrated in any particular subcellular compartment. We suggest that NECABs represent a novel family of regulatory Ca(2+)-binding proteins with an unusual domain structure and a limited expression in a subclass of neurons.
authors.affiliation: Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sugita
authors.forename: A
authors.initials: A
authors.lastname: Ho
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D003001:Cloning, Molecular; D005136:Eye Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution
chemical_list: D002135:Calcium-Binding Proteins; D005136:Eye Proteins; C438750:NECAB2 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger