a b s t r a c tLeucine-rich repeat and fibronectin type III domain-containing (LRFN) family proteins are thought to be neuronal-specific proteins that play essential roles in neurite outgrowth and synapse formation. Here, we focused on expression and function of LRFN4, the fourth member of the LRFN family, in non-neural tissues. We found that LRFN4 was expressed in a wide variety of cancer and leukemia cell lines. We also found that expression of LRFN4 in the monocytic cell line THP-1 and in primary monocytes was upregulated following macrophage differentiation. Furthermore, we demonstrated that LRFN4 signaling regulated both the transendothelial migration of THP-1 cells and the elongation of THP-1 cells via actin cytoskeleton reorganization. Our data indicate that LRFN4 signaling plays an important role in the migration of monocytes/macrophages.
a b s t r a c tWe previously reported that leucine-rich repeat and fibronectin type III domain-containing 4 (LRFN4) functioned in migration and morphological change (i.e.cell elongation) of monocytic cells. Here, we examined a molecular mechanism regulating LRFN4-mediated cell elongation. We found that 14-3-3 and NCK proteins complexed with LRFN4, and they were involved in LRFN4-mediated cell elongation. We also identified the regions of LRFN4 interacting with NCK1 and 14-3-3s. Finally, we demonstrated that a Rac1 small GTPase was involved in LRFN4-mediated cell elongation. These results indicated that LRFN4 complexed with 14-3-3s and NCK1 to mediate elongation in monocytic cells via Rac-1-mediated actin cytoskeleton reorganization.
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