During epithelial collective migration, partial tissue organization is maintained through cell adhesion. The developing C. elegans male gonad undergoes a collective cell migration consisting of the linker cell, which acts as a leader migratory cell, and a chain of interconnected epithelial-like follower cells. This organization differs from the hermaphrodite gonad, in which the leader cells are immediately followed by germ cells. We have identified a conserved protein, LNKN-1, required for maintaining cell adhesion during male gonadal migration. LNKN-1 defines the LINKIN proteins, a family of previously uncharacterized single-pass transmembrane proteins conserved from unicellular eukaryotes to humans. We identified seven atypical FG-GAP domains in the extracellular domain, which potentially fold into a β-propeller structure resembling the ligand-binding domain of α-integrins. By antibody staining and YFP-translational fusion, we observe expression of LNKN-1 in the plasma membrane of all gonadal cells with apical and lateral enrichment. Through rescue experiments, we showed that both the extracellular and intracellular domains are required for LNKN-1 function. We identified RUVB-1/RUVBL1, RUVB-2/RUVBL2 and TBA-2/α-tubulin as interactors of LINKIN by mass spectrometry using SILAC-treated HEK 293T cells and testing candidates for lnkn-1-like phenotypes in C. elegans male gonad migration. We propose that LINKIN promotes tissue cohesion during migration by adhering through a β-propeller extracellular domain and regulating microtubule dynamics through RUVBL proteins at its intracellular domain. We are currently building on the LINKIN pathway by investigating whether LINKIN binds homophilically or has a heterophilic binding partner. Additionally, we are examining other lnkn-1 mutants, including a point mutation of a highly conserved residue and a new LINKIN deletion mutant.
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