Phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks, or PI4P5Ks) are a class of

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

that

phosphorylate In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

phosphatidylinositol 4-phosphate Phosphatidylinositol-4-phosphate (PtdIns4''P'', PI-4-P, PI4P, or PIP) is a precursor of phosphatidylinositol (4,5)-bisphosphate. PtdIns4''P'' is prevalent in the membrane of the Golgi apparatus. In the Golgi apparatus, PtdIns4''P'' binds to the G ...

. They perform this reaction on the fifth

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

of the

myo-inositol In biochemistry, medicine, and related sciences, inositol generally refers to ''myo''-inositol (formerly ''meso''-inositol), the most important stereoisomer of the chemical compound cyclohexane-1,2,3,4,5,6-hexol. Its formula is ; the molecule has ...

ring to form

phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...

Function

Phosphatidylinositol Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...

Phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

-5

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

(PI4P5K) or PIP5K or PI5K family regulates diverse cellular processes such as

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

(GPCR) signaling, vesicle trafficking,

chemotaxis Chemotaxis (from ''chemical substance, chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell organism, single-cell or multicellular organisms direct thei ...

and cellular movement. There are at least two types of PIP5K found which includes Type I and Type II. Reinvestigation of the substrate specificity of PI(4)P5Ks, however, revealed that the type II PI(4)P5Ks catalyze phosphorylation of a novel phosphoinositide phosphati- dylinositol 5-phosphate at the D-4 position of the inositol ring, leading to the revised conclusion that the type II enzymes are actually phosphatidylinositol 5-phosphate 4-kinases. Thus, the PI(4)P5K family now comprises just the type I􏰂.Other types are also suspected in the nervous system but have not been well reported. These enzyme synthesize diverse Phosphatidyl Inositol 4,5 bisphosphate ( PI(4,5)P2 ) by phosphorylating the D- 5 position of the inositol ring of Phosphatidylinositol 4-phosphate]. PIP5KI is the most extensively studied and is synthesizing for most of the Phosphatidylinositol 4,5-bisphosphate, PI(4,5)P2 pool the cell. Type I phosphatidylinositol-4-phosphate 5-kinase (PIP5KI) are further classified as PIP5Kα, PIP5Kβ and PIP5Kγ on the basis of their basic differences in primary structure and the variation in the expression level in different compartment of cells, indicating that individual PIP5KI isoform has non identical function Moreover, PIP5Kγ, has three splicing variance; PIP5Kγ635, PIP5γ661, and PIP5Kγ687, making it one of the key regulators for producing PI(4,5)P2 that plays a role in diverse cellular processes. Although an extensive study to elucidate the role of PI(4,5)P2 and PIP5 kinase has been focused on many cellular processes such as vesicle trafficking, cell movement and cytoskeletal assembly, a very few studies have been reported for their role in neuronal development. PIP5K is highly expressed kinase in the nervous system of several organisms and plays important role in neuronal development including embryogenesis and post-natal neural development. The disruption of PIP5KIγ leads to broad developmental and cellular defects in mice indicating PIP5KIγ plays critical role for embryogenesis and adulthood of mice and its disruption causes fatality for postnatal life ">ref name=":2"> The embryo without PIP5KIγ has extensive prenatal lethality during embryonic development. The disruption of PIP5KIγ also causes neural tube closure defects caused by decreased PI(4,5)P2 level. In contrast to this, mice lacking PIPKIα or PIPKIβ have major impact during adulthood but no effect in prenatal embryo, Even in the absence of both PIPKIα and PIPKIβ, a single allele of PIPKIγ, can support normal the adulthood functioning, indicating PIPKIγ and PIPKIα have partially overlapping function during embryogenesis. In different experiments, the role of PIP5K in neurite outgrowth has been analyzed by knocking down PIP5Kα. The Nerve Growth Factor (NGF) induced neurite outgrowth was more obvious in knock down cells than in control cells. In contrary, the over-expression of PIP5Ka in to a PIP5Ka Knock down cells abrogated

neurite outgrowth A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...

showing PIP5K acts as a negative regulator of NGF-induced neurite outgrowth through inhibiting the PI3K/ AKT signaling pathway in PC12 cells. A novel mechanism for the role of PIPKIα in regulating neuronal morphology by controlling microtubule dynamics is reported in mouse. During axon pathfinding, a growth cone is formed to guide the migrating

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

Growth cone A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago ...

formation is induced by Kinesin Supar Family protein 2A (KIF2A)

KIF2A Kinesin-like protein KIF2A is a protein that in humans is encoded by the ''KIF2A'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that ...

- mediated depolymerization of microtubules. The interaction of PIPKα with KIF2A suppresses the elongation of axon branches. In association with Daam2, PIP5 kinase promotes

Wnt signaling In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...

and receptor complex formation which is required for the regenerative myelination of the neuron. In the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(CNS) of chick, PIP5K-PI(4,5)P2 mediated role of Daam2 has been reported for the development of neurons.

List of PIP4Ks

* Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha (PIP4K2A) * Phosphatidylinositol-5-phosphate 4-kinase type-2 beta (PIP4K2B) * Phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4K2C)

References

{{Reflist Phospholipids