High impact information on PHLDB2

• This interaction could co-localize heterologously expressed gamma-filamin with GFP-LL5beta in the unidentified vesicles [1].
• Importantly, pleckstrin homology domain mutants of LL5beta that could not bind PtdIns(3,4,5)P(3) were constitutively localized to this vesicle population [1].
• In addition, expression of platelet-derived growth factor-receptor mutants unable to activate type 1A phosphoinositide 3-kinase (PI3K) or serum starvation in porcine aortic endothelial cells lead to redistribution of LL5beta to this vesicle population [1].
• Strikingly, a substantial proportion of LL5beta became associated with an unidentified intracellular vesicle population in the context of low PtdIns(3,4,5)P(3) levels produced by the addition of wortmannin or LY294002 [1].
• Three of the novel proteins (TMEM16A, PHLDB2 and ARHGAP21) were analysed further to show that they have the potential to be developed as therapeutic targets [2].

Biological context of PHLDB2

• LL5beta 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 [3].

Anatomical context of PHLDB2

• CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5beta [3].
• LL5beta is required for cortical CLASP accumulation and microtubule stabilization in HeLa cells, while ELKS plays an accessory role in these processes [3].
• Cortical clusters of LL5beta and ELKS do not overlap with focal adhesions but often form in their vicinity and can affect their size [3].
• Work in this issue of Developmental Cell identifies the protein LL5beta as a key CLASP binding platform that mediates communication between the cell cortex and the microtubule cytoskeleton [4].
• LL5beta 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 [3].

References