The intracellular localisation and mobility of Type Iγ phosphatidylinositol 4P 5‐kinase splice variants

Abstract

There are three known splice variants of Type Iγ phosphatidylinositol 4-phosphate 5-kinase (PIPkin Iγ): PIPkins Iγ87, Iγ90, and the most recently cloned (Giudici, M.L., Emson, P.C. and Irvine, R.F. (2004) A novel neuronal-specific splice variant of Type I phosphatidylinositol 4-phosphate 5-kinase isoform gamma. Biochem. J. 379, 489–496) PIPkin IγC (here called PIPkin Iγ93). Here, we have explored the subcellular localisation and mobility of Type I PIPkins in transfected cells by confocal microscopy and flourescence recovery after photobleaching. The unique behaviour shown by PIPkin Iγ93 is consistent with its suggested distinct function. Moreover, the markedly different localisation and mobility of active versus inactive PIPkin Iγ93 provide insights into the factors that dictate cellular targeting of Type Iγ PIPkins.

PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions

“…Indeed, overexpressed kinase-inactive PIP5Ks often do not localise strongly to the plasma membrane (Giudici et al, 2006). A notable exception, however, is that overexpressed rat PIP5K688 was reported to localise to an intracellular membrane compartment (Giudici et al, 2006). Therefore, it is clear that there is nonoverlapping localisation of the different isoforms, suggesting that they have different cellular functions.…”

“…PIP5K628 also has a deletion between amino acids 347-407. Indeed, overexpressed kinase-inactive PIP5Ks often do not localise strongly to the plasma membrane (Giudici et al, 2006). A notable exception, however, is that overexpressed rat PIP5K688 was reported to localise to an intracellular membrane compartment (Giudici et al, 2006).…”

“…This isoform is also present at adherens junctions in epithelial cells, where it colocalises with cadherin . Surprisingly, unlike mouse PIP5K661, rat PIP5K688 (also known as PIP5KC) is not present at focal contacts, even though it contains the same 26 aminoacid residues that are thought to be important for the targeting of PIP5K661 to this location (Giudici et al, 2006). Although visualisation of endogenous PIP5K suggests that the various isoforms are differentially localised, overexpressed GFP-labelled PIP5Ks localise strongly at the plasma membrane.…”

Type Iγ phosphatidylinositol phosphate kinase targets to the centrosome and restrains centriole duplication

“…To date, six alternatively spliced isoforms of PIPKIc have been reported (Giudici et al, 2004;Giudici et al, 2006;Ishihara et al, 1998;Schill and Anderson, 2009;Xia et al, 2011). PIPKIc isoforms are targeted to distinct subcellular sites.…”

Comparative phenotypic analysis of the two major splice isoforms of phosphatidylinositol phosphate kinase type Iγ in vivo

“…human PIPKIa is mouse PIPKIb, and vice versa); in this work the mouse nomenclature will be used exclusively. PIPKIs have distinct subcellular localization which likely contributes to their specificity of function (Doughman et al, 2003;Giudici et al, 2006). Furthermore, PIPKIc is expressed as a variety of different splice variants with distinct subcellular localization patterns (Ishihara et al, 1998;Giudici et al, 2004;Schill and Anderson, 2009;Xia et al, 2011).…”