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The impact of PI 5-phosphatases on phosphoinositides in cell function and human disease.

par Ramos, Ana Raquel ;Ghosh, Somadri ;Erneux, Christophe
Référence Journal of lipid research
Publication Publié, 2018-09

Article révisé par les pairs

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Résumé :

Phosphoinositides (PIs) are recognized as major signaling molecules in many different functions of eukaryotic cells. PIs can be dephosphorylated by multiple phosphatase activities at the 5-, 4- and 3- positions. Human PI 5-phosphatases belong to a family of 10 members. Except for INPP5A, they all catalyze the dephosphorylation of PI(4,5)P2 and/or PI(3,4,5)P3 at the 5- position. PI 5-phosphatases thus directly control the levels of PI(3,4,5)P3 and also participate in fine-tuning regulatory mechanisms of PI(3,4)P2 and PI(4,5)P2. Second messenger functions have been demonstrated for PI(3,4)P2 in invadopodium maturation and in lamellipodia formation. PI 5-phosphatases can use several substrates on isolated enzymes, and it has been challenging to establish their real substrate in vivo. PI(4,5)P2 has multiple functions in signaling, including interaction with scaffold proteins, ion channels, and cytoskeleton proteins. PI 5-phosphatase isoenzymes have been individually implicated in human diseases, such as the oculocerebrorenal syndrome of Lowe, through mechanisms which include lipid-controlling. Oncogenic and tumor suppressive functions of PI 5-phosphatases have also been reported in different cell contexts. The mechanisms responsible for genetic diseases and for tumor suppressor or oncogenic functions are not fully understood. The regulation of PI 5-phosphatases is thus crucial in understanding cell functions.