Skip to main content

The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo.

Publication ,  Journal Article
Martemyanov, KA; Lishko, PV; Calero, N; Keresztes, G; Sokolov, M; Strissel, KJ; Leskov, IB; Hopp, JA; Kolesnikov, AV; Chen, C-K; Lem, J ...
Published in: J Neurosci
November 12, 2003

DEP (for Disheveled, EGL-10, Pleckstrin) homology domains are present in numerous signaling proteins, including many in the nervous system, but their function remains mostly elusive. We report that the DEP domain of a photoreceptor-specific signaling protein, RGS9 (for regulator of G-protein signaling 9), plays an essential role in RGS9 delivery to the intracellular compartment of its functioning, the rod outer segment. We generated a transgenic mouse in which RGS9 was replaced by its mutant lacking the DEP domain. We then used a combination of the quantitative technique of serial tangential sectioning-Western blotting with electrophysiological recordings to demonstrate that mutant RGS9 is expressed in rods in the normal amount but is completely excluded from the outer segments. The delivery of RGS9 to rod outer segments is likely to be mediated by the DEP domain interaction with a transmembrane protein, R9AP (for RGS9 anchoring protein), known to anchor RGS9 on the surface of photoreceptor membranes and to potentiate RGS9 catalytic activity. We show that both of these functions are also abolished as the result of the DEP domain deletion. These findings indicate that a novel function of the DEP domain is to target a signaling protein to a specific compartment of a highly polarized neuron. Interestingly, sequence analysis of R9AP reveals the presence of a conserved R-SNARE (for soluble N-ethylmaleimide-sensitive factor attachment protein receptor) motif and a predicted overall structural homology with SNARE proteins involved in vesicular trafficking and fusion. This presents the possibility that DEP domains might serve to target various DEP-containing proteins to the sites of their intracellular action via interactions with the members of extended SNARE protein family.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

November 12, 2003

Volume

23

Issue

32

Start / End Page

10175 / 10181

Location

United States

Related Subject Headings

  • Subcellular Fractions
  • Retina
  • RGS Proteins
  • Protein Structure, Tertiary
  • Photic Stimulation
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Macromolecular Substances
  • In Vitro Techniques
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Martemyanov, K. A., Lishko, P. V., Calero, N., Keresztes, G., Sokolov, M., Strissel, K. J., … Arshavsky, V. Y. (2003). The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo. J Neurosci, 23(32), 10175–10181. https://doi.org/10.1523/JNEUROSCI.23-32-10175.2003
Martemyanov, Kirill A., Polina V. Lishko, Nidia Calero, Gabor Keresztes, Maxim Sokolov, Katherine J. Strissel, Ilya B. Leskov, et al. “The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo.J Neurosci 23, no. 32 (November 12, 2003): 10175–81. https://doi.org/10.1523/JNEUROSCI.23-32-10175.2003.
Martemyanov KA, Lishko PV, Calero N, Keresztes G, Sokolov M, Strissel KJ, et al. The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo. J Neurosci. 2003 Nov 12;23(32):10175–81.
Martemyanov, Kirill A., et al. “The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo.J Neurosci, vol. 23, no. 32, Nov. 2003, pp. 10175–81. Pubmed, doi:10.1523/JNEUROSCI.23-32-10175.2003.
Martemyanov KA, Lishko PV, Calero N, Keresztes G, Sokolov M, Strissel KJ, Leskov IB, Hopp JA, Kolesnikov AV, Chen C-K, Lem J, Heller S, Burns ME, Arshavsky VY. The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo. J Neurosci. 2003 Nov 12;23(32):10175–10181.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

November 12, 2003

Volume

23

Issue

32

Start / End Page

10175 / 10181

Location

United States

Related Subject Headings

  • Subcellular Fractions
  • Retina
  • RGS Proteins
  • Protein Structure, Tertiary
  • Photic Stimulation
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Macromolecular Substances
  • In Vitro Techniques