Short communication Expression of gec1/GABARAPL1 versus GABARAP mRNAs in human: predominance of gec1/GABARAPL1 in the central nervous system Christophe Nemos, Virginie Mansuy, Sandrine Vernier-Magnin, Annick Fraichard, Miche `le Jouvenot * , Re ´gis Delage-Mourroux Laboratoire de Biochimie-Biologie Mole ´culaire, Universite ´ de Franche-Comte ´, U.F.R. Sciences et Techniques, 16 route de Gray, 25030 Besanc ßon cedex, France Accepted 18 September 2003 Abstract GABARAP and gec1/GABARAPL1 genes encode very similar proteins belonging to a new microtubule-associated protein (MAP) family. These proteins could participate in a complex clustering, targeting and/or degrading the GABA A receptors on post-synaptic membrane of neurons. Using specific cDNA probes, we investigated the differential expression of both genes in 76 human tissues. Against all odds, gec1/ GABARAPL1 was more expressed than GABARAP in the central nervous system (CNS), while GABARAP was more expressed in endocrine glands. D 2003 Elsevier B.V. All rights reserved. Theme: Cellular and molecular biology Topic: Gene structure and function: general Keywords: gec1/GABARAPL1; GABARAP; Gene expression; Macroarray; Human; Central nervous system Understanding the mechanisms involved in the intracel- lular trafficking and the clustering of inhibitory neurotrans- mitter GABA A receptors on GABAergic synapses in the central nervous system (CNS) is fundamental because they are implicated in various phenomenons such as mental disorders as well as sleep and mood regulation [3]. GABA receptors are ubiquitously expressed in the CNS, possibly on every single neuron [3]. They are also present in several non-neuronal tissues, including the such endocrine organs as the pituitary gland, pancreas and testis [1,2]. Thus, the research of the potential protein partners of GABA A recep- tors constitutes an important stage to establish its physiol- ogy and/or pathophysiology. GABA A -receptor-associated protein (GABARAP) is the first protein identified that interacts with g2 subunit of GABA A receptor [8]. This 14-kDa protein was then shown as being the partner of gephyrin and N-ethylmaleimide-sensitive factor (NSF). It has been proposed that GABARAP together with gephyrin could participate in a protein complex clustering, targeting and/or degrading the ligand-gated ion channels GABA A receptors on post-synaptic membrane of neurons [5]. How- ever, the study of Green et al. [4] demonstrated specific interaction of the cytoplasmic domain of transferrin receptor (TfR) with GABARAP and it was suggested that GABARAP plays a more general role outside the confines of neuronal cells and GABA A receptors. These authors also reported, using anti-GABARAP polyclonal antibodies, cross-reactivity with other family members. In fact, GABARAP belongs to a new microtubule-associated pro- tein (MAP) family in which GEC1/GABARAPL1 is the only one having very strong identity and similarity with GABARAP (87% and 94%, respectively). GEC1/GABAR- APL1 could be the best candidate to explain the cross- reactivity observed by Green et al. Gec1/GABARAPL1 and GABARAP genes are located on 12p12.3 and 17p13.12 human chromosomes, respectively, and could be differentially regulated in different tissues [9]. Indeed, there is no similarity between 3V untranslated re- gions (3VUTR) of these genes and software analysis of both genes and their flanking regions reveals different putative cis-regulatory elements. In particular, a potential estrogen 0169-328X/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.molbrainres.2003.09.011 * Corresponding author. Tel.: +33-3-81-66-65-40; fax: +33-3-81-66- 62-67. E-mail address: michele.jouvenot@univ-fcomte.fr (M. Jouvenot). www.elsevier.com/locate/molbrainres Molecular Brain Research 119 (2003) 216 – 219