In 1996 Mary Kennedy and colleagues isolated the protein Densin-180 from the rbat postsynaptic density1. This protein had a unique structure, in that it contained a set of leucine-rich repeats (LRRs) as well as a PSD-95/Dlg/ZO-1 (PDZ) domain; these domains are thought to mediate protein–protein interactions. Recently, further proteins containing both types of domain have been isolated from fly2, worm3, mouse4 and human4,5. It seems an opportune time to select a collective name for this family of proteins.
We endorse the name ‘LAP (LRR And PDZ domain) proteins’ for proteins with this structure. We emphasize that the individual proteins will not be renamed. The known LAP proteins contain 16 canonical LRRs located at the amino terminus of the protein, as well as a conserved, LRR-like region immediately carboxy-terminal to the LRRs. The LRRs from LAP proteins are more closely related to each other than to LRRs from other proteins. The known LAP proteins also contain either one or four PDZ domains. It may be useful to distinguish between these subfamilies by using the designations ‘LAP1’ and ‘LAP4’ respectively.
Amongst eukaryotes for which complete genomic sequence is available, Saccharomyces cerevisiae (in which both LRR and PDZ domains can be found) contains no LAP proteins. Caenorhabditis elegans contains a single LAP1 protein, Let-413 (Ref. 4), whereas Drosophila contains both a LAP1 protein, dLAP1 (GenBank AAF58179), and a LAP4 protein, Scribble2 (two alternative splice variants, GenBank AF190774 and AJ271647). Vertebrates are likely to contain at least three LAP proteins, as the LAP1 proteins Densin-180 (Ref. 2) and Erbin4 are both found in rat, whereas human hScribble2,5 (two variants, GenBank AF271734 and AF240677) is a LAP4 protein. Further vertebrate LAP proteins may be identified as complete genomic sequence becomes available.
Although analyses of these proteins are just beginning, one striking feature is their polarized localization along the cell membrane. This localization, in conjunction with the modular arrangement of the protein–protein interaction domains they contain, is consistent with genetic and molecular analyses indicating that LAP proteins may play a key role in regulating the subcellular distribution of other proteins. Identification and further studies of LAP proteins will reveal what aspects of function, as well as of structure, are conserved within this family.
Apperson et al. J. Neurosci. 16, 6389–6352 (1996).
Bilder, D. & Perrimon, N. Nature 403, 676–680 (2000).
Legouis, R. et al. Nature Cell Biol. 2, 415– 422 (2000).
Borg, J-P. et al. Nature Cell Biol. 2, 407–414 (2000).
Nagase et al. DNA Res. 2, 167–174 (1995).
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Bilder, D., Birnbaum, D., Borg, JP. et al. Collective nomenclature for LAP proteins. Nat Cell Biol 2, E114 (2000). https://doi.org/10.1038/35017119
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