Apathway from the extracellular matrix to the actin cytoskeleton sucks dendritic spines back into the body of the neuron, say Wing-Yu Fu, Yu Chen, Nancy Ip (Hong Kong University of Science and Technology, Hong Kong), and colleagues.
Spines come and go as synapses remodel during memory formation. Extracellular cues for remodeling eventually cause actin reorganization. Ip's group has now pieced together an entire pathway from cell surface receptor to the actin that causes spine retraction.
The pathway starts with ephrin-A1 whose receptor, EphA4, is a known negative regulator of spine formation. The authors show that ephrin-A1–EphA4 interaction activates Cdk5. This kinase then phosphorylates ephexin1, a guanine nucleotide exchange factor for RhoA GTPase, which probably pulls in the spines by activating actomyosin contraction.
Disruption of this pathway via Cdk5 mutation resulted in abnormal spine morphogenesis and an inability to retract spines in response to ephrin-A1.
Ip speculates that Cdk5 may also be involved in regulating EphB-mediated spine protrusion. As spine dynamics ultimately influences the efficiency of synaptic transmission, it is important to understand the precise roles of Cdk5 in spine growth and retraction.