Make or break - Switches, structure and shape.

1. Making The Right Play

   Clearly, there exists a fine balancing act between inhibitory and activation processes within the cell, calling for a high level of co-ordination between the switches. The group has determined that many of the proteins associated with these switches have multiple domains which enable them, in addition to performing their individual functions, to communicate with each other and with other pathways. This extensive co-operativity ensures that the cell is either in, or acquires, the right shape to respond to external stimuli which convey the changing demands of the organism. The development of the nervous system involves the morphological differentiation of neurons, whose proper shaping is essential to synapse formation and other aspects of networking. Generation and loss of neurons also occur throughout this development while changes in cellular associations are required for neuronal plasticity, all seemingly guided by trophic factors some of which activate the Rho signaling pathways. The Glaxo-IMCB group has observed, as with the kinases, that the classical neurotransmitter acetylcholine can exhibit another function – it activates Cdc42 and Rac, which then execute their morphological function. How trophic factors and proteins, capable of multiple functions, act so specifically is certainly a matter of timing and of being in the right place.