Synaptotagmin: is 2 better than 1?

Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more information on the format and purpose of the Journal Club, please see Review of Pang et al. The synaptotagmin protein family, characterized by two C-terminal calcium-binding motifs, is expressed throughout the brain (Grise et al., 2007). Synap-totagmin-1, the best characterized member , acts as a calcium sensor in the Ca 2ϩ-dependent release of neurotransmitter vesicles (Geppert et al., 1994) and is necessary for calcium-dependent exocytosis in invertebrates (Littleton et al., 1993). However, knockout studies in mice demonstrated that synaptotagmin-1 was necessary for one type of Ca 2ϩ-dependent exocytosis (fast, synchronous release), but not for another type (asynchronous release) (Geppert et al., 1994). Of the synap-totagmin family, synaptotagmin-2 exhibits the highest degree of homology with synaptotagmin-1. Indeed, synap-totagmin-2 can rescue synaptotagmin-1 deficiency, and its expression overlaps partially but not completely with synaptotagmin-1 (Geppert et al., 1994; Nagy et al., 2006). In a recent Journal of Neuroscience article , Pang et al. (2006) generated a synaptotagmin-2 knockout mouse to examine the expression and function of synaptotagmin-2. Pang et al. (2006) characterized the expression pattern of the protein, the consequences of deletion on survival, and the electrophysiological properties of synaptotagmin-2-deficient neurons in the forebrain and neuromus-cular junction (Table 1). The authors inserted LacZ in the exon-2 region of the synaptotagmin-2 gene, allowing them to simultaneously examine the expression of synaptotagmin-2 and the consequences of its deletion. The expression of other synaptic vesicle proteins was not altered except for a slight upregulation of synaptotagmin-1 in the spinal cord [Pang et al. The knockout mice exhibited motor dysfunction and reduced body weight and growth and survived no longer than 24 d after birth, a survival length similar to that of synaptotagmin-1-deficient mice [Pang et al. expression of synaptotagmin-1 at the neu-romuscular junction is initially sufficient to maintain synaptic transmission in the absence of synaptotagmin-2. However it would be interesting to know the time course of expression of the two proteins as the mice mature. For example, early expression of synaptotagmin-1 could initially compensate for the absent synapto-tagmin-2 but then be switched off later in development. Synaptotagmin-2 was expressed heavily in the brainstem and spinal cord but only weakly in forebrain. Expression was confined to only a few areas …