PAFAH1B1 Antibody – Rabbit Polyclonal

This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [provided by RefSeq, Apr 2009]

PAFAH1B1: Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet- activating factor (PAF) by removing the acetyl group at the SN-2 position. Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Defects in PAFAH1B1 are the cause of lissencephaly type 1 (LIS1); also known as classic lissencephaly. LIS1 is characterized by agyria or pachgyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. LIS1 is associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum. Defects in PAFAH1B1 are the cause of subcortical band heterotopia (SBH). SBH is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric ribbons of gray matter found in the central white matter between the cortex and the ventricular surface. Defects in PAFAH1B1 are a cause of Miller-Dieker lissencephaly syndrome (MDLS). MDLS is a contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition. Belongs to the WD repeat LIS1/nudF family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Cell cycle regulation; Lipid Metabolism - ether lipid

Chromosomal Location of Human Ortholog: 17p13.3

Cellular Component: astral microtubule; centrosome; nuclear membrane; leading edge; nuclear envelope; cell cortex; cytosol; kinetochore; kinesin complex; microtubule associated complex; growth cone; cell soma; axon; perinuclear region of cytoplasm; motile primary cilium

Molecular Function: heparin binding; dynein binding; protein binding; protein homodimerization activity; phospholipase binding; microtubule binding; dynein intermediate chain binding; phosphoprotein binding

Biological Process: acrosome formation; negative regulation of JNK cascade; platelet activating factor metabolic process; adult locomotory behavior; stem cell division; positive regulation of axon extension; protein secretion; neuron migration; positive regulation of mitotic cell cycle; retrograde axon cargo transport; microtubule-based process; cerebral cortex neuron differentiation; synaptic transmission; learning and/or memory; establishment of centrosome localization; establishment of mitotic spindle orientation; vesicle transport along microtubule; brain morphogenesis; G2/M transition of mitotic cell cycle; neuromuscular process controlling balance; layer formation in the cerebral cortex; microtubule organizing center organization and biogenesis; mitosis; organelle organization and biogenesis; corpus callosum morphogenesis; hippocampus development; transmission of nerve impulse; nuclear envelope disassembly; microtubule cytoskeleton organization and biogenesis; ameboidal cell migration; neuroblast proliferation; cerebral cortex development; mitotic cell cycle; actin cytoskeleton organization and biogenesis; positive regulation of cytokine and chemokine mediated signaling pathway; nuclear migration; lipid catabolic process

Disease: Lissencephaly 1