The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain

Stephani E. Renick, Daniel T Kleven, June Chan, Katinka Stenius, Teresa A. Milner, Virginia M. Pickel, Robert T. Fremeau

Research output: Contribution to journalArticle

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Abstract

The expression of a brain-specific high-affinity Na+-dependent (and Cl--dependent) L-proline transporter (PROT) in subpopulations of putative glutamatergic neurons in mammalian brain suggests a physiological role for this carrier in excitatory neurotransmission (Fremeau et al., 1992). To gain insights into potential sites where PROT may function, we used a C-terminal domain antipeptide antibody to determine the regional distribution and subcellular localization of PROT in rat forebrain. PROT immunoreactivity was seen in processes having a regional light microscopic distribution comparable to that of known glutamatergic projections within the cortex, caudate putamen nucleus (CPN), hippocampal formation, and other forebrain regions. In all regions examined by electron microscopy (cortex, CPN, and the stratum oriens of CA1), PROT labeling was observed primarily within subpopulations of axon terminals forming asymmetric excitatory-type synapses. Immunogold labeling for PROT was detected in close contact with membranes of small synaptic vesicles (SSVs) and more rarely with the plasma membrane in these axon terminals. Subcellular fractionation studies confirmed the preferential distribution of PROT to synaptic vesicles. The topology of PROT in synaptic vesicles was found to be inverted with respect to the plasma membrane, suggesting that PROT-containing vesicles are generated by a process involving endocytosis from the plasma membrane. Because PROT lacks any of the known characteristics of other vesicular transporters; these results suggest that certain excitatory terminals have a reserve pool of PROT associated with SSVs. The delivery of PROT to the plasma membrane by exocytosis could play a critical role in the plasticity of certain glutamatergic pathways.

Original languageEnglish (US)
Pages (from-to)21-33
Number of pages13
JournalJournal of Neuroscience
Volume19
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Synaptic Vesicles
Prosencephalon
Proline
Brain
Cell Membrane
Caudate Nucleus
Putamen
Presynaptic Terminals
proline transporter
Exocytosis
Endocytosis
Synaptic Transmission
Synapses
Hippocampus
Electron Microscopy

Keywords

  • Electron microscopy
  • Excitatory amino acids
  • Excitatory neurotransmission
  • L- proline
  • Neurotransmitter transporter
  • Presynaptic nerve terminal
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain. / Renick, Stephani E.; Kleven, Daniel T; Chan, June; Stenius, Katinka; Milner, Teresa A.; Pickel, Virginia M.; Fremeau, Robert T.

In: Journal of Neuroscience, Vol. 19, No. 1, 01.01.1999, p. 21-33.

Research output: Contribution to journalArticle

Renick, Stephani E. ; Kleven, Daniel T ; Chan, June ; Stenius, Katinka ; Milner, Teresa A. ; Pickel, Virginia M. ; Fremeau, Robert T. / The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 1. pp. 21-33.
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