The specific interaction of phosphoinositides with proteins is critical for a plethora of cellular processes, including cytoskeleton remodelling, mitogenic signalling, ion channel regulation and membrane traffic. The spatiotemporal restriction of different phosphoinositide species helps to define compartments within the cell, and this is particularly important for membrane trafficking within both the secretory and endocytic pathways. Phosphoinositide homoeostasis is tightly regulated by a large number of inositol kinases and phosphatases, which respectively phosphorylate and dephosphorylate distinct phosphoinositide species. Many of these enzymes have been implicated in regulating membrane trafficking and, accordingly, their dysregulation has been linked to a number of human diseases. In the present review, we focus on the inositol phosphatases, concentrating on their roles in membrane trafficking and the human diseases with which they have been associated.
- human disease
- inositol phosphatase
- membrane traffic
- secretory pathway
Abbreviations: Aβ, amyloid β-peptide; AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; AP, adaptor protein; CCP, clathrin-coated pit; CMT, Charcot–Marie–Tooth; EGFR, epidermal growth factor receptor; ER, endoplasmic reticulum; ERGIC, endoplasmic reticulum–Golgi intermediate compartment; GLUT4, glucose transporter type 4; INPP4, inositol polyphosphate 4-phosphatase; INPP5, inositol polyphosphate 5-phosphatase; LAMP2, lysosome-associated membrane protein 2; MORM, mental retardation, truncal obesity, retinal dystrophy and micropenis; MTM, myotubularin; MTMR, myotubularin-related; MVB, multivesicular body; NMDAR, N-methyl-D-aspartate receptor; OCRL, oculocerebrorenal syndrome of Lowe; PI3K, phosphoinositide 3-kinase; PIPP, proline-rich inositol polyphosphate 5-phosphatase; PM, plasma membrane; PTEN, phosphatase and tensin homologue deleted on chromosome 10; SAC, suppressor of actin; SH2, Src homology 2; SHIP, SH2 domain-containing inositol 5-phosphatase; SKIP, skeletal muscle and kidney inositol phosphatase; SNP, single nucleotide polymorphism; SNX9, sorting nexin 9; SYNJ, synaptojanin; TGN, trans-Golgi network; TMEM55, transmembrane protein 55; T-tubule, transverse tubule; Vps, vacuolar protein sorting; XLCNM, X-linked recessive form of centronuclear myopathy; YVS, Yunis–Varón syndrome
- © The Authors Journal compilation © 2014 Biochemical Society