Effect of polyanions and polycations on detyrosination of tubulin and microtubules at steady state.
Microtubule protein preparations purified from rat brain were used to study the effect of polycations and polyanions on the release of the COOH-terminal tyrosine of the alpha-chain of tubulin catalyzed by tubulin carboxypeptidase. (1) Most of the polycations and polyanions tested, independently of the ionogenic group, inhibited the reaction in a concentration-dependent fashion. Under steady-state conditions, detyrosination of the microtubule pool was inhibited to the same degree as occurred with the non-assembled tubulin pool, except in the case of chondroitin sulphate. This compound inhibited detyrosination of the non-assembled tubulin pool, but not that of microtubules. (2) Heparin, the most potent inhibitor tested, produced the dissociation of the carboxypeptidase from microtubules. Many, but not all, of the other microtubule-associated polypeptides were also dissociated by heparin. (3) Polylysine counteracted the inhibitory and dissociating effects of heparin. (4) Heparin protected tubulin carboxypeptidase against inactivation. Our results and previous reports describing, in nervous tissue, the presence of proteoglycans, RNA and basic proteins that inhibit detyrosination, suggest that tubulin carboxypeptidase might be physiologically modulated by electrically charged macromolecules.
Centro de Investigaciones en Química Biológica de Córdoba, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Argentina.
R A
RA
Lopez
C A
CA
Arce
H S
HS
Barra
D000818:Animals; D000838:Anions; D001921:Brain / Q000201:enzymology; D002268:Carboxypeptidases / Q000378:metabolism*; D002412:Cations; D002809:Chondroitin Sulfates / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008868:Microtubule Proteins / Q000378:metabolism*; D011061:Poly A / Q000494:pharmacology; D011099:Polyglutamic Acid / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D014404:Tubulin / Q000378:metabolism*
D000838:Anions; D002412:Cations; D008868:Microtubule Proteins; D011479:Protamines; D014404:Tubulin; D011061:Poly A; D011107:Polylysine; D011099:Polyglutamic Acid; D006493:Heparin; D002809:Chondroitin Sulfates; D002268:Carboxypeptidases; C023212:tyrosyltubulin carboxypeptidase