Disease relevance of FGD4

• We report that disruption of frabin/FGD4, a GEF for the Rho GTPase cell-division cycle 42 (Cdc42), causes peripheral nerve demyelination in patients with autosomal recessive Charcot-Marie-Tooth (CMT) neuropathy [1].

High impact information on FGD4

• The cellular expression of either a dominant negative mutant of PI3K (PI3K-Deltap85) or functionally deficient mutants of frabin inhibited C. parvum-induced Cdc42 accumulation at the host cell-parasite interface [2].
• Frabin having ABD was associated with the actin cytoskeleton, whereas frabin lacking ABD was diffusely distributed in the cytoplasm [3].
• Full-length frabin induces microspike formation and c-Jun N-terminal kinase (JNK) activation [3].
• Association of frabin with the actin cytoskeleton is essential for microspike formation through activation of Cdc42 small G protein [3].
• Frabin furthermore induces indirect activation of Rac small G protein (Rac) in intact cells [4].

Anatomical context of FGD4

• RESULTS: Frabin induces the formation of microspikes at the basal area of the lateral membranes through the activation of Cdc42 and Rac in MDCK cells, although a dominant active mutant of Cdc42 or Rac alone, or both, did not induce the formation of microspikes [4].

Associations of FGD4 with chemical compounds

• Frabin also was recruited to the host cell-parasite interface, a process inhibited by two PI3K inhibitors, wortmannin and LY294002 [2].

Other interactions of FGD4

• Phosphatidylinositol 3-kinase and frabin mediate Cryptosporidium parvum cellular invasion via activation of Cdc42 [2].

References