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Results indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes Charcot-Marie-Tooth disease or lower motor neuron disease affecting the function of neurons and glial cells.
Recruitment of Syx to the cell membrane, the selective activation of Dia1 signaling, coupled with the suppression of ROCK and actin reorganization, plays a key role in establishing cell polarity during directed cell migration.
This study identifies compound heterozygous PLEKHG5 mutations as the cause of recessive intermediate Charcot-Marie-Tooth disease.
a novel means of regulating junctional Syx localization and function by phosphorylation-induced 14-3-3 (show YWHAQ Proteins) binding and further support the importance of Syx function in maintaining stable cell-cell contacts.
We identified a homozygous missense mutation (c.1940 T-->C [p.647 Phe-->Ser (show SIGLEC1 Proteins)]) of the Pleckstrin (show PLEK Proteins) homology domain-containing, family G member 5 gene (show GPD1 Proteins), PLEKHG5, in families with lower motor neuron disease.
Data show that pleckstrin (show PLEK Proteins) homology containing family member 5 (Plekhg5)-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active ras-related protein Rab-26 (Rab26 (show RAB26 Proteins)).
Plekhg5 affects cell polarity, migration, adhesion, degradation, and podosome organization in macrophages and osteoclasts.
VEGF (show VEGFA Proteins) causes translocation of Syx from cell junctions, promoting junction disassembly, whereas angiopoietin 1 (show ANGPT1 Proteins) maintains Syx at the junctions, inducing junction stabilization.
a well defined Rnd3 (show RND3 Proteins) effector Syx
This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene.
pleckstrin homology domain containing, family G (with RhoGef domain) member 5
, pleckstrin homology domain containing family G member 5
, pleckstrin homology domain-containing family G member 5-like
, NFkB activating protein
, PH domain-containing family G member 5
, guanine nucleotide exchange factor 720
, novel PH domain-containing protein
, pleckstrin homology domain-containing family G member 5
, synectin-binding guanine exchange factor
, RhoA-specific guanine exchange factor SYX1
, RhoA-specific guanine exchange factor SYX2
, synectin-binding RhoA exchange factor
, neuronal RhoA GEF protein
, transcript highly enriched in cortex and hippocampus