Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies

Table 1

Rho GTPase modulators in mental disorders.

Protein	Gene	GTPase signaling	Clinical features	Effect of mutation on spine morphogenesis	Interaction with Shank
Oligophrenin 1	OPHN1	GAP for Rac1/Cdc42/RhoA	Intellectual disability, microcephaly, ataxia, hypersensitivity	↓ on spine length and maturation	Indirect via Homer
MEGAP	MEGAP	GAP for Rac1/Cdc42	Microcephaly, facial disfigurement	Loss of filopodia and lamellipodia	Not known
RICH2	ARHGAP44	GAP for Rac1/Cdc42	No mutation yet identified in human	↑ spine area, multiple spines fused together	Direct
αPIX	ARHGEF6	GEF for Rac1/Cdc42	Intellectual disability	↓ spine with mushroom morphology	Not known
βPIX	ARHGEF7	GEF for Rac1/Cdc42	No mutation yet identified in human	↓ synaptic proteins, defective NMJ	Direct
Alsin	ALS2	GEF for Rac1, Rab5, Ran	Motor neuron degeneration	↓ axon growth, ↑ cell death	Not known