C. elegans LAR phosphatase PTP-3

Receptor-like protein-tyrosine phosphatases (RPTPs) form a diverse family of transmembrane enzymes that play roles in cell adhesion and cell signaling (Brady-Kalnay and Tonks, 1995; den Hertog et al., 1999). The LAR (Leukocyte Common Antigen Related) protein is the founding member of a subfamily of RPTPs known as type IIa RPTPs, defined by extracellular domains composed of immunoglobulin-like and fibronectin type III (FNIII) domains. The extracellular domain of LAR thus resembles those of cell adhesion proteins such as N-CAM, implying that it links cell adhesion and intracellular tyrosine phosphorylation. Vertebrate genomes contain at least three LAR-like RPTP genes: LAR, PTPδ, and PTPσ. All three generate multiple protein isoforms by tissue-specific alternative splicing, and are expressed in complex patterns in many ectodermal and endodermal epithelia and in neural tissues (Pulido et al., 1995; Stoker and Dutta, 1998). In non-neuronal cells LAR family members localize to focal adhesions (Serra-Pagès et al., 1995), adherens junctions (Aicher et al., 1997) and regions in contact with basal laminae. In neurons, LAR family members are found on cell bodies, processes and growth cones, suggesting a role in modulating cell adhesion during axon outgrowth (Zhang et al., 1998; Zhang and Longo, 1995). The Drosophila LAR ortholog Lar (previously known as Dlar), is mostly expressed in the nervous system (Krueger et al., 1996), although expression in oogenesis has also been observed (Fitzpatrick et al., 1995). The most detailed analysis of RPTP function in vivo has been in Drosophila. In mutants lacking Lar some motor axons bypass their correct target area, reflecting a failure in defasciculation at the point where the axons choose to extend into the muscle (Krueger et al., 1996). Lar is also required for normal target recognition by axons from retinal photoreceptors; in Lar mutants, these axons retract from their normal target layer, suggesting a role for Lar in recognition or adhesion to target layer cells (Clandinin et al., 2001; MaurelZaffran et al., 2001). Different defasciculation or outgrowth defects are seen in fly mutants lacking other RPTPs (Desai et al., 1996; Garrity et al., 1999; Sun et al., 2000a). The axonal phenotypes observed in Lar mutants are incompletely penetrant, likely because other RPTPs can substitute for loss of Lar function (Desai et al., 1997). Thus, in Drosophila, Lar functions to modulate cell adhesion during axon growth; several likely components of the Lar pathway have recently been identified based on their interactions with Lar in growth cone guidance (Bateman et al., 2000; Wills et al., 1999). Lar 2141 Development 129, 2141-2153 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV8917