Cellular localization of synaptotagmin I, II, and III mRNAs in the central nervous system and pituitary and adrenal glands of the rat

Abstract

Three isoforms of synaptotagmin, a synaptic vesicle protein involved in neurotransmitter release, have been characterized in the rat, although functional differences between these isoforms have not been reported. In situ hybridization was used to define the localization of synaptotagmin I, II, and III transcripts in the rat CNS and pituitary and adrenal glands. Each of the three synaptotagmin genes has a unique expression pattern. The synaptotagmin III gene is expressed in most neurons, but transcripts are much less abundant than the products of the synaptotagmin I and II genes. A majority of neurons in the forebrain expressed both synaptotagmin I and III mRNAs while synaptotagmin II gene expression was confined to subsets of neurons in layers IV-VI of the cerebral cortex, in the dentate granule cell region, the hilus, and the CA1-CA3 areas of the hippocampus. In the cerebellum, all three transcripts were visualized in the granule cell layer. Furthermore, synaptotagmin I probes revealed striking differences between distinct populations of neurons, as in addition to moderate labeling of granule cells, much more prominent hybridization signals were detected on scattered cell bodies likely to be Golgi interneurons. In the most caudal part of the brain, synaptotagmin II transcripts were abundant and were coexpressed with synaptotagmin III mRNAs. This pattern was found in putative motoneurons of the spinal cord, suggesting that the two isoforms might be involved in exocytosis at the neuromuscular junction. Only synaptotagmin I mRNAs were detected in the anterior and intermediate pituitary and in adrenal medullary cells. These data reveal an unexpectedly subtle segregation of the expression of synaptotagmin genes and the existence of multiple combinations of synaptotagmin isoforms which may provide diversity in the regulation of neurosecretion.

Exocytotic protein components in rat pituitary gland after long-term estrogen administration

“…In recent years, a group of protein components of the exocytotic machinery has been shown to be present in the rat anterior pituitary gland (Wendland & Scheller 1994, Marquéze et al 1995, Oho et al 1995, Redecker et al 1995, Aguado et al 1996, Jacobsson & Meister 1996. The amount and immunocytochemical location of all of these proteins shown in the present study agrees with previous reports.…”

“…However, a functional role for these proteins and their non-neuronal isoforms has been proposed in different endocrine cell types (Lang et al 1997, Morgan & Burgoyne 1997). These molecular components of the exocytotic machinery have also been identified in anterior pituitary cells (Wendland & Scheller 1994, Marquéze et al 1995, Oho et al 1995, Redecker et al 1995, Aguado et al 1996, Jacobsson & Meister 1996, Majó et al 1998. In adenohypophyseal cells, t-SNAREs are located at the plasma membrane, and protein components of neuronal secretory organelle membranes are located on hormone-containing secretory granules and synaptic-like microvesicles (SLMV) (Wendland & Scheller 1994, Aguado et al 1996, Jacobsson & Meister 1996, Majó et al 1998.…”

Interneuron Transcriptional Dysregulation Causes Frequency-Dependent Alterations in the Balance of Inhibition and Excitation in Hippocampus

“…Immunohistochemistry also showed that complexin 1 expression is reduced throughout CA1 in PGC-1␣ Ϫ/Ϫ mice (data not shown). These large reductions in synaptotagmin 2 and complexin 1 in hippocampus are consistent with the fact that, within the hippocampus, these transcripts are primarily expressed by GABAergic interneurons (Marquèze et al, 1995;Eastwood et al, 2000).…”

Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses

“…Second, recombinant expression of synaptotagmin revealed that synaptotagmin 2 can act as a fast Ca 2ϩ sensor and functionally replace synaptotagmin 1 (16). Finally, expression of synaptotagmin 2 mRNA and protein was previously demonstrated in scattered neurons in the hilus (20,33) and immunolabeling with the antibody znp-1 (presumably recognizing synaptotagmin 2) was found in presynaptic terminals located on somata of CA1 hippocampal pyramidal neurons (34).…”

“…The functional role of the other synaptotagmins has remained unclear. Synaptotagmins are differentially expressed in central neurons (16,19,20) and differ in kinetic properties (21). Thus, it is possible that differential expression of synaptotagmins determines the time course of transmitter release and the proportion of synchronous and asynchronous release at different synapses (6,(22)(23)(24).…”