Neurons consist of specialised subcellular compartments, the axons, dendrites and synapses, that are characterised by specific morphologies and cytoskeletal elements. Yi-Ping Hsueh and colleagues have previously reported that the neuron-specific cortactin-binding protein 2 (CTTNBP2) regulates the mobility of cortactin and striatin (the regulatory subunit of protein phosphatase 2A) in dendritic spines and, through the resulting effects on the actin cytoskeleton, controls dendritic spine formation and maintenance. In this work (p. 3521), the authors now show that, unexpectedly, CTTNBP2 also binds to and stabilises microtubules in COS cells and in cultured hippocampal neurons, thereby regulating dendritic arborisation. They then demonstrate that the middle region of CTTNBP2 is necessary and sufficient for microtubule binding; however, the N-terminal domain, which contains a coiled-coiled motif (NCC) and mediates CTTNBP2 oligomerisation, is required for microtubule bundling. Accordingly, the knockdown of CTTNBP2 or the expression of only its middle or NCC domains impairs dendritic arborisation. Taken together, these data provide the first example of a neuron-specific factor that controls both the actin cytoskeleton and microtubules. Furthermore, because mutations in CTTNBP2 have recently been associated with autism spectrum disorders, the results presented here might also lead to further insights into the underlying causes of these neurodevelopmental disorders.

© 2014. Published by The Company of Biologists Ltd
2014