Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies were raised against synthetic peptides corresponding to several regions of the rat brain gamma-aminobutyric acid (GABA) transporter. According to our model, this glycoprotein has 12 transmembrane alpha-helices with both amino and carboxyl termini located in the cytoplasm. The antibodies recognized the intact transporter on Western blots. Upon papain treatment, a reconstitutively active transporter can be isolated upon lectin chromatography (Kanner, B. I., Keynan, S., and Radian, R. (1989) Biochemistry 28, 3722-3728). The papainized transporter runs on sodium dodecyl sulfate-polyacrylamide gels as a broad band with an apparent molecular mass between about 58 and 68 kDa as compared to 80 kDa for the untreated transporter. The transporter fragment was recognized by all the antibodies, except for that raised against the amino terminus. Pronase cleaves the transporter to a relatively sharp 60-kDa band, which reacts with the antibodies against the internal loops but not with either the amino- or the carboxyl-terminal. This pronase-treated transporter, upon isolation by lectin chromatography, was reconstituted. It exhibits full GABA transport activity. This activity exhibits the same features as the intact system including an absolute dependence on sodium and chloride as well as electrogenicity. We conclude that the amino- and carboxyl-terminal parts of the transporter, possibly including transmembrane alpha-helices 1, 2, and 12, are not required for the transport function.
 ...
PMID:Neither amino nor carboxyl termini are required for function of the sodium- and chloride-coupled gamma-aminobutyric acid transporter from rat brain. 173 54

The sodium- and chloride-coupled gamma-aminobutyric transporter, an 80-kDa glycoprotein, has been subjected to deglycosylation and limited proteolysis. The treatment of the 80-kDa band with endoglycosidase F results in its disappearance and reveals the presence of a polypeptide with an apparent molecular mass of about 60 kDa, which is devoid of 125I-labeled wheat germ agglutinin binding activity but is nevertheless recognized by the antibodies against the 80-kDa band. Upon limited proteolysis with papain or Pronase, the 80-kDa band was degraded to one with an apparent molecular mass of about 60 kDa. This polypeptide still contains the 125I-labeled wheat germ agglutinin binding activity but is not recognized by the antibody. The effect of proteolysis on function was examined. The transporter was purified by use of all steps except that for the lectin chromatography [Radian, R., Bendahan, A., & Kanner, B.I. (1986) J. Biol. Chem. 261, 15437-15441]. After papain treatment and lectin chromatography, gamma-aminobutyric transport activity was eluted with N-acetylglucosamine. The characteristics of transport were the same as those of the pure transporter, but the preparation contained instead of the 80-kDa polypeptide two fragments of about 66 and 60 kDa. The ability of the anti-80-kDa antibody to recognize these fragments was relatively low. The observations indicate that the transporter contains exposed domains which are not important for function.
 ...
PMID:Structural and functional studies on the sodium- and chloride-coupled gamma-aminobutyric acid transporter: deglycosylation and limited proteolysis. 250 69