Liptins, a family of LAR transmembrane protein-tyrosine phosphatase- interacting proteins

Abstract

LAR family transmembrane protein-tyrosine phos. phatases function in axon guidance and mammary gland development. In cultured cells, LAR binds to the intracellular, coiled coil LAR-interacting protein at discrete ends of focal adhesions, implicating these proteins in the regulation of cell-matrix interactions. We describe seven LAR-interacting protein-like genes in humans and Caenorhabditis elegans that form the liprin gene family. Based on sequence similarities and binding characteristics, liprins are subdivided into α-type and β-type Hprins. The C-terminal, non-coiled coil regions of α-liprins bind to the membrane-distal phosphatase domains of LAR family members, as well as to the C-terminal, non-coiled coil region of β-liprins. Both α- and β-liptins homodimerize via their N-terminal, coiled coil regions. Liptins are thus multivalent proteins that potentially form complex structures. Some liptins have broad mRNA tissue distributions, whereas others are predominately expressed in the brain. Co-expression studies indicate that liprin-α2 alters LAR cellular localization and induces LAR clustering. We propose that liprins function to localize LAR family tyrosine phosphatases at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.