FIG 9.

Model of the interplay between CLC, CLF-1, CNTFRα, and sorLA. (A) The cytokine subunits CLC and CLF-1 each contain a single site for CNTFRα binding and bind with moderate affinity (thin arrows). The assembled heterodimer CLC:CLF-1 contains two binding sites (one in each subunit), which together generate a bonus effect and a high affinity for CNTFRα (thick arrow). CLF-1 further harbors an independent site for binding to sorLA and binds sorLA alone or in complex with other subunits. (B) sorLA conveys endocytosis of the tripartite complex CLC:CLF-1:CNTFRα via binding to CLF-1. Following internalization, CNTFRα and CLC:CLF-1 are sorted to lysosomal degradation while sorLA is recycled. (C) sorLA may enhance signaling, notably in CNTFRα-deficient cells, by binding and concentrating complexes of CLC:CLF-1 and sCNTFRα on the cell membrane.