CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5β

CLASPs are mammalian microtubule-stabilizing proteins that can mediate the interaction between distal microtubule ends and the cell cortex. Using mass spectrometry-based assays, we have identified two CLASP partners, LL5 beta and ELKS. LL5 beta and ELKS form a complex that colocalizes with CLASPS at the cortex of HeLa cells as well as at the leading edge of motile fibroblasts. LL5 beta is required for cortical CLASP accumulation and microtubule stabilization in HeLa cells, while ELKS plays an accessory role in these processes. LL5 beta is a phosphatidylinositol-3,4,5-triphosphate (PIP3) binding protein, and its recruitment to the cell cortex is influenced by PI3 kinase activity but does not require intact microtubules. Cortical clusters of LL5 beta and ELKS do not overlap with focal adhesions but often form in their vicinity and can affect their size. We propose that LL5 beta and ELKS can form a PIP3-regulated cortical platform to which CLASPs attach distal microtubule ends.