= ligands - secreted GPI ancchored . . - Nervous system+axon, immune, vascular, organogenesis - Most semaphorin KOs = embryonically lethal - KDs - different axon branching Structure - Sema domain - PSI domain - Ig-like domain - Plexin structure - Sema -.. - dimerization - semaphorin dimer + 2 plexins - Plexin autoinhibition - extracellular- big rings - intracellular domains cant get near each other - Plexin-plexin interaction doesn`t activate -Neuropilin - necessary for plexin-semaphorin binding
Intracellular signaling - lpexni intracellular domain - juxtadomain - RBD - binds G-proteins (Rho...) - gap - gtpase - in active conformation - RBD exposed and can bind Raps - GAP domain inactivates Rap - MICAL - F-actin depolymerization (Met oxidation) - monooxygenase domain - oxidation - CC domain - inhibits MO
Autosomal dominant lateral temporal epilepsy - Mical G150 + R915 interaction - disruption causes symptons -hyperactive mical Kallmann`s syndrome - Sema3 - known malignnant mutAtions - outside of interface - misfolding Hrschprung disease - intestine obstruction - lack of specific neurons