Nomenclature of EAAT-2 (GLT-1) splice variants by David Pow.
Since the original description of GLT-1 (human nomenclature = EAAT-2) by Pines et al (1992), a number of alternate splice variants have been descibed and different nomenclatures have been used. The PDF diagram here from Rauen et al., 2004 (link here ), summarizes the nomenclature to date.
Data from the recent paper by Rozyczka and Engele (2005) have not yet been added into this schema but this will be done shortly.
The schematic illustrations in the lower resolution figure (below) and sequences (see end of page) of the rat and mouse forms of GLT-1 are depicted. The mouse and rat sequences are almost identical.
The original form of GLT-1 is depicted first, with the order of the new forms and nomenclatures added in approximately the timeline of use or publication. References and Genebank accesssion # are included.
Subsequent to the original descriptions of rat and mouse sequences of GLT-1, Utsunomiya-Tate and co-workers have described two splice variants, bearing the prefix "m" to denote mouse. These variant forms were denoted mGLT-1A and mGLT-1B respectively. These differed from the original mouse and rat forms in that they were alternately spliced at both the carboxyl and amino terminal regions. Both clones were originally identified from a brain cDNA library, suggesting they may be expressed in brain, but Utsunomiya-Tate et al have suggested that the N-terminal splicing is probably most prevalent in liver.
A nomenclature issue subsequently arose; many papers have used GLT-1 as a generic term, without defining the splice variant that was being studied. Chen and co-workers chose to use the term GLT-1a when describing the original splice form, whilst our group (Pow and co-workers), chose to use the suffix "alpha" ie GLT-1alpha (normally written with the alpha symbol, but spelt in full here due to use of default fonts in most web browsers), to avoid confusion with the different protein described earlier as GLT-1A. by Utsunomiya-Tate and co-workers.
Chen and co-workers have described a C-terminal splice variant of GLT-1. This has the same C-terminus as the Utsunomiya-Tate et al. GLT-1B protein but diffes at the amino terminus. Chen et al have described this as GLT-1b. A different nomenclature has been used by Schmitt et al., 2002, , who in describing the same protein, have used the term GLT-1v, where "v" denotes variant. We have adopted the use of GLT-1v in our studies (eg see Sullivan et al., 2004), to avoid the confusion between GLT-1B and GLT-1b that is otherwise likely to arise in the literature.
Discrimination of GLT-1 splice variants:
Antibodies directed against the carboxyl terminal regions of GLT-1 have been used to distinguish GLT-1a from GLT-1B/b/v. Used alone, they cannot distinguish which N-terminal splicing is expressed by a protein, thus they cannot distinguish GLT-1B from 1b/1v. Accordingly references in the literature to the immunocytochemical detection of one of these forms, should be interpreted as potentially identifying either of the two alternate N-terminal splicings unless otherwise proven using N-terminal specific antibodies directed against either of the two N-terminal splice sequences.
GLT-1C
A recent collaborative study by the Rauen and Pow labs has identified a new splice variant, GLT-1C which is the "missing" neuronal presynaptic GLT-1 splice variant in the retina (Rauen et al., Neurochemistry international, 2004 (link here) Click here for images from the paper showing its presynaptic localisation.
A variety of human splice variants have also been defined by Meyer and co-workers but it is unclear at this stage if any are translated into functional proteins. The latter group have discussed these splicings and others in relation to human disease.
Pines et al., 1992 Rat GLT-1 sequence
MASTEGANNMPKQVEVRMHDSHLSSEEPKHRNLGMRMCDKLGKNLLLSLTVFGVILGAVCGGLLR
LAAPIHPDVVMLIAFPGDILMRMLKMLILPLIISSLITGLSGLDAKASGRLGTRAMVYYMSTTIIAAVLG
VILVLAIHPGNPKLKKQLGPGKKNDEVSSLDAFLDLIRNLFPENLVQACFQQIQTVTKKVLVAPPSEE
ANTTKAVISLLNETMNEAPEETKIVIKKGLEFKDGMNVLGLIGFFIAFGIAMGKMGEQAKLMVEFFNI
LNEIVMKLVIMIMWYSPLGIACLICGKIIAIKDLEVVARQLGMYMITVIVGLIIHGGIFLPLIYFVVTRKNP
FSFFAGIFQAWITALGTASSAGTLPVTFRCLEDNLGIDKRVTRFVLPVGATINMDGTALYEAVAAIFIAQ
MNGVILDGGQIVTVSLTATLASIGAASIPSAGLVTMLLILTAVGLPTEDISLLVAVDWLLDRMRTSVNVV
GDSFGAGIVYHLSKSELDTIDSQHRMHEDIEMTKTQSVYDDTKNHRESNSNQCVYAAHNSVVIDECKVT
LAANGKSADCSVEEEPWKREK
Mukainaka et al., 1995 Mouse sequence GLT-1
MASTEGANNMPKQVEVRMHDSHLSSDEPKHRNLGMRMCDKLGKNLLLSLTVFGVILGAVCGGLLR
LASPIHPDVVMLIAFPGDILMRMLKMLILPLIISSLITGLSGLDAKASGRLGTRAMVYYMSTTIIAAVLG
VILVLAIHPGNPKLKKQLGPGKKNDEVSSLDAFLDLIRNLFPENLVQACFQQIQTVTKKVLVAPPSEE
ANTTKAVISMLNETMNEAPEETKIVIKKGLEFKDGMNVLGLIGFFIAFGIAMGKMGEQAKLMVEFFNI
LNEIVMKLVIMIMWYSPLGIACLICGKIIAIKDLEVVARQLGMYMITVIVGLIIHGGIFLPLIYFVVTRKNP
FSFFAGIFQAWITALGTASSAGTLPVTFRCLEDNLGIDKRVTRFVLPVGATINMDGTALYEAVAAIFIAQ
MNGVILDGGQIVTVSLTATLASIGAASIPSAGLVTMLLILTAVGLPTEDISLLVAVDWLLDRMRTSVNVV
GDSFGAGIVYHLSKSELDTIDSQHRMQEDIEMTKTQSIYDDKNHRESNSNQCVYAAHNSVVIDECKVT
LAANGKSADCSVEEEPWKREK
If you wish to comment on the interpretations below please email us (mail@eaats.org) and we will append your views.