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Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors.

Publication ,  Journal Article
Valdés, V; Valenzuela, JI; Salas, DA; Jaureguiberry-Bravo, M; Otero, C; Thiede, C; Schmidt, CF; Couve, A
Published in: PloS one
January 2012

In neuronal cells the intracellular trafficking machinery controls the availability of neurotransmitter receptors at the plasma membrane, which is a critical determinant of synaptic strength. Metabotropic γ amino-butyric acid (GABA) type B receptors (GABA(B)Rs) are neurotransmitter receptors that modulate synaptic transmission by mediating the slow and prolonged responses to GABA. GABA(B)Rs are obligatory heteromers constituted by two subunits, GABA(B)R1 and GABA(B)R2. GABA(B)R1a and GABA(B)R1b are the most abundant subunit variants. GABA(B)R1b is located in the somatodendritic domain whereas GABA(B)R1a is additionally targeted to the axon. Sushi domains located at the N-terminus of GABA(B)R1a constitute the only difference between both variants and are necessary and sufficient for axonal targeting. The precise targeting machinery and the organelles involved in sorting and transport have not been described. Here we demonstrate that GABA(B)Rs require the Golgi apparatus for plasma membrane delivery but that axonal sorting and targeting of GABA(B)R1a operate in a pre-Golgi compartment. In the axon GABA(B)R1a subunits are enriched in the endoplasmic reticulum (ER), and their dynamic behavior and colocalization with other secretory organelles like the ER-to-Golgi intermediate compartment (ERGIC) suggest that they employ a local secretory route. The transport of axonal GABA(B)R1a is microtubule-dependent and kinesin-1, a molecular motor of the kinesin family, determines axonal localization. Considering that progression of GABA(B)Rs through the secretory pathway is regulated by an ER retention motif our data contribute to understand the role of the axonal ER in non-canonical sorting and targeting of neurotransmitter receptors.

Duke Scholars

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2012

Volume

7

Issue

8

Start / End Page

e44168

Related Subject Headings

  • Receptors, GABA-B
  • Rats, Sprague-Dawley
  • Rats
  • Protein Transport
  • Molecular Sequence Data
  • Mice
  • Kinesins
  • Golgi Apparatus
  • General Science & Technology
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Valdés, V., Valenzuela, J. I., Salas, D. A., Jaureguiberry-Bravo, M., Otero, C., Thiede, C., … Couve, A. (2012). Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors. PloS One, 7(8), e44168. https://doi.org/10.1371/journal.pone.0044168
Valdés, Viviana, José Ignacio Valenzuela, Daniela A. Salas, Matías Jaureguiberry-Bravo, Carolina Otero, Christina Thiede, Christoph F. Schmidt, and Andrés Couve. “Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors.PloS One 7, no. 8 (January 2012): e44168. https://doi.org/10.1371/journal.pone.0044168.
Valdés V, Valenzuela JI, Salas DA, Jaureguiberry-Bravo M, Otero C, Thiede C, et al. Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors. PloS one. 2012 Jan;7(8):e44168.
Valdés, Viviana, et al. “Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors.PloS One, vol. 7, no. 8, Jan. 2012, p. e44168. Epmc, doi:10.1371/journal.pone.0044168.
Valdés V, Valenzuela JI, Salas DA, Jaureguiberry-Bravo M, Otero C, Thiede C, Schmidt CF, Couve A. Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors. PloS one. 2012 Jan;7(8):e44168.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2012

Volume

7

Issue

8

Start / End Page

e44168

Related Subject Headings

  • Receptors, GABA-B
  • Rats, Sprague-Dawley
  • Rats
  • Protein Transport
  • Molecular Sequence Data
  • Mice
  • Kinesins
  • Golgi Apparatus
  • General Science & Technology
  • Female