This Week in The Journal
Cellular/MolecularSynaptotagmin Isoforms, Aplysia-Style
Differential Regulation of Transmitter Release by Alternatively Spliced Forms of Synaptotagmin I
Arash Nakhost, Gry Houeland, Vincent F. Castellucci, and Wayne S. Sossin
(see pages 6238-6244)
Synaptotagmins are the principle Ca2+-sensing proteins that trigger vesicle fusion and release of neurotransmitters. In the course of investigating synaptotagmin function in Aplysia, Nakhost et al. identified a novel splice variant of synaptotagmin I (Syt I). The Syt IVQ isoform is named for a pair of amino acids inserted in the juxtamembrane linker between the transmembrane domain and the calcium-binding C2 domains. The linker region is conserved across evolution within Syt I-like isoforms and contains all of the Syt I phosphorylation sites. Aplysia neurons expressed approximately equal amounts of the two isoforms of Syt I, and both were phosphorylated by protein kinase C (PKC). However, transfection of neurons with fluorescently labeled Syt I and Syt IVQ revealed interesting functional differences. Rapid stimulation of Aplysia sensory neurons leads to synaptic depression, which can be reversed by serotonin-mediated activation of a PKC signaling cascade. This reversal was blocked in synapses expressing Syt IVQ by a mechanism upstream of PKC phosphorylation. Although it remains unclear just how splicing of the juxtamembrane linker affects synaptic function, the authors consider whether the linker might regulate sorting in the trans-Golgi network and thus affect trafficking of serotonin receptors.
Development/Plasticity/Repair
Putting Some Muscle into Dendrites
Actin Filament-Stabilizing Protein Tropomyosin Regulates the Size of Dendritic Fields
Wenjun Li and Fen-Biao Gao
(see pages 6171-6175)
The dendritic arbor of a neuron is one of its most recognizable and characteristic features. Cell–cell interactions as well as cell-intrinsic factors during development must play a role in this pattern formation; consider for example how easily one distinguishes a Purkinje cell from a dorsal root ganglion neuron in vivo or in vitro. How cellular factors specify the complex shape and size patterns is still primarily unknown. In this week's Journal, Li and Gao used a genetic screen to look for molecules involved in dendrite formation in the dorsal cluster neurons of the Drosophila peripheral nervous system. They previously identified a dendritic overextension phenotype with mutants in a gene, suitably named flamingo. Flamingo has the structure of a membrane receptor, probably involved in cell–cell interactions. They now report that loss-of-function mutants of the neural isoform of the actin-stabilizing protein tropomyosin II have a similar phenotype. The phenotype was cell-autonomous, based on a method [mosaic analysis with a repressible cell marker (MARCM)] that allows visualization of single mutant neurons in a mosaic animal. Overextension of dendrites was further enhanced when both genes were silenced. These results indicate that actin cytoskeletal dynamics can play a key role in dendrite formation.
Behavioral/Systems/Cognitive
Taking the Green Line to the Brainstem
Purkinje Cell Synapses Target Physiologically Unique Brainstem Neurons
Chris Sekirnjak, Bryce Vissel, Jacob Bollinger, Michael Faulstich, and Sascha du Lac
(see pages 6392-6398)
Identifying neurons within a functional circuit is relatively easy when neurons are tightly packed together. But once in a while, sets of target cells are not so obviously grouped. Such is the case with the neurons involved in the vestibulo-ocular reflex (VOR), the circuit that allows for image stabilization on the retina during head movement. Most cerebellar Purkinje cells synapse onto neurons of the deep cerebellar nuclei (DCN). The VOR circuit, however, takes a detour to the brainstem, where Purkinje neurons from the floccular lobe synapse on floccular target neurons (FTNs) scattered in the ventrolateral part of the medial vestibular nucleus. These neurons have been difficult to identify, but Sekirnjak et al. take advantage of the L7 promoter to achieve Purkinje cell-specific expression of tau-green fluorescent protein (GFP). Green Purkinje axons allowed easy identification of postsynaptic FTNs in the brainstem. The FTN firing patterns were unusual for brainstem neurons but resembled Purkinje-targeted neurons in the DCN. The characteristic rapid spontaneous firing and postinhibitory rebound spiking suggest that these electrophysiological signatures may be critical in cerebellar control of motor learning.
