Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction - PubMed (original) (raw)

Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction

H Wang et al. J Neurochem. 2000 Aug.

Free article

Abstract

GABA(A) receptor-associated protein (GABARAP) was isolated on the basis of its interaction with the gamma2 subunit of GABA(A) receptors. It has sequence similarity to light chain 3 (LC3) of microtubule-associated proteins 1A and 1B. This suggests that GABARAP may link GABA(A) receptors to the cytoskeleton. GABARAP associates with tubulin in vitro. However, little is known about the mechanism for the interaction, and it is not clear whether the interaction occurs in vivo. Here, we report that GABARAP interacts directly with both tubulin and microtubules in a salt-sensitive manner, indicating the association is mediated by ionic interactions. GABARAP coimmunoprecipitates with tubulin and associates with both microtubules and microfilaments in intact cells. The cellular distribution is altered by treatment with taxol, nocodazole, and cytochalasin D. The tubulin binding domain was located at the N terminus of GABARAP by using synthetic peptides and deletion constructs and is marked by a specific arrangement of basic amino acids. The interaction between GABARAP and actin might be mediated by other proteins. These results demonstrate the GABARAP interacts with the cytoskeleton both in vitro and in cells and suggest a role of GABARAP in the interaction between GABA(A) receptors and the cytoskeleton. Such interactions are presumably needed for receptor trafficking, anchoring, and/or synaptic clustering. The structural arrangement of the basic amino acids present in the tubulin binding domain of GABARAP may aid in recognition of the potential of tubulin binding activity in other known proteins.

PubMed Disclaimer

Cited by

GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons.
Leil TA, Chen ZW, Chang CS, Olsen RW. Leil TA, et al. J Neurosci. 2004 Dec 15;24(50):11429-38. doi: 10.1523/JNEUROSCI.3355-04.2004. J Neurosci. 2004. PMID: 15601949 Free PMC article.
The PX-RICS-14-3-3zeta/theta complex couples N-cadherin-beta-catenin with dynein-dynactin to mediate its export from the endoplasmic reticulum.
Nakamura T, Hayashi T, Mimori-Kiyosue Y, Sakaue F, Matsuura K, Iemura S, Natsume T, Akiyama T. Nakamura T, et al. J Biol Chem. 2010 May 21;285(21):16145-54. doi: 10.1074/jbc.M109.081315. Epub 2010 Mar 22. J Biol Chem. 2010. PMID: 20308060 Free PMC article.
The possible role of GABAA receptors and gephyrin in epileptogenesis.
González MI. González MI. Front Cell Neurosci. 2013 Jul 22;7:113. doi: 10.3389/fncel.2013.00113. eCollection 2013. Front Cell Neurosci. 2013. PMID: 23885234 Free PMC article.
Activity-dependent expression of acyl-coenzyme a-binding protein in retinal muller glial cells evoked by optokinetic stimulation.
Barmack NH, Bilderback TR, Liu H, Qian Z, Yakhnitsa V. Barmack NH, et al. J Neurosci. 2004 Feb 4;24(5):1023-33. doi: 10.1523/JNEUROSCI.3936-03.2004. J Neurosci. 2004. PMID: 14762120 Free PMC article.
Sequence-specific 1H, 13C and 15N resonance assignments of human GABA receptor associated protein.
Stangler T, Mayr LM, Dingley AJ, Luge C, Willbold D. Stangler T, et al. J Biomol NMR. 2001 Oct;21(2):183-4. doi: 10.1023/a:1012416810974. J Biomol NMR. 2001. PMID: 11727985 No abstract available.

Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction - PubMed (original) (raw)