PAFAH1B1 : platelet activating factor acetylhydrolase 1b regulatory subunit 1

Description

The PAFAH1B1 (platelet activating factor acetylhydrolase 1b regulatory subunit 1) is a protein-coding gene located on chromosome 17.

The PAFAH1B1 gene (also known as LIS1) provides instructions for making a protein that is one part (subunit) of a complex called platelet activating factor acetyl hydrolase 1B (PAFAH1B). This complex regulates the amount of a molecule called platelet activating factor (PAF) in the brain. PAF is thought to be involved in directing the movement (migration) of nerve cells (neurons), a process known as neuronal migration. Proper neuronal migration is essential for normal brain development and function.Separate from its role in the PAFAH1B complex, the PAFAH1B1 protein is also likely involved in the organization of the cell's structural framework (the cytoskeleton). This protein interacts with microtubules and regulates the activity of a variety of proteins that are involved in their function. Microtubules are rigid, hollow fibers that make up the cytoskeleton, and they are involved in cell division and movement

The PAFAH1B1 protein serves as a regulatory subunit (beta subunit) in the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) enzyme, which breaks down PAF and similar molecules. This regulatory role involves controlling the enzyme's activity based on the composition of the catalytic dimer. It is essential for the proper activation of Rho GTPases and actin polymerization in migrating cerebellar and hippocampal neurons, triggered by calcium influx through NMDA receptors. PAFAH1B1 also positively regulates the minus-end directed microtubule motor protein dynein, potentially enhancing dynein-mediated microtubule sliding by directing dynein to the microtubule plus end. This protein is crucial for various dynein- and microtubule-dependent processes like maintaining Golgi integrity, transporting microtubule fragments peripherally, and connecting the nucleus with the centrosome. During brain development, PAFAH1B1 is required for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone towards the cortical plate. This migration involves nucleokinesis, where migrating cells extend an anterior process into which the nucleus subsequently translocates. Dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. PAFAH1B1 could also play a role in other forms of cell locomotion like fibroblast migration during wound healing. It is necessary for dynein recruitment to microtubule plus ends and BICD2-bound cargos. The protein may modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR.

PAFAH1B1 is also known as LIS1, LIS2, MDCR, MDS, NudF, PAFAH.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing