Regulation of the dynamin GTPase cycle

D. E. Warnock, S. B. Muhlberg, S. Sever, S. L. Schmid

Research output: Contribution to journalArticle

Abstract

Dynamin GTPase activity is required for late stages in endocytic coated vesicle formation. We have compared the biochemical properties of the neuronspecific isoform, dynamin-I (dynI) with those of the ubiquitously expressed isoform, dynamin-II (dynlI) and found that the endogenous rate of GTP hydrolysis by dynll was ten-[bid that of dynI. This was not due to differences in affinity for GTP as determined by kinetic analyses or measured directly by' fluorescence anisotropy using Mant-derivatized guanine nucleotides. Instead. the major factors affecting increased specific activity of dynlI GTPase were its greater propensity for selgassernbly and the increased stability of assembled dynlI to GTP-triggered disassembly. Deletion of the C-terminal Pro/Arg-rich domain (/deltaPRD) from either isoform abolished self-assembly and assemblydependent increases in GTP hydrolysis. The two/deltaPRD isoforms exhibited sinfilar intrinsic (;'['Pase. These results were consistent with our previous hypothesis that self-assembly is the major regulator of dynamin GTPase activity and that the intrinsic rate of GTP hydrolysis reflects a dynamic. GTPdependent equilibrium of assembly and disassembly. Using limited proteolysis to dissect dynamin into structural domains, we have identified a region between the PH domain and the C-terminal PRI), termed the GTPase effector domain (GEl)). that is required for the high intrinsic rates of GTP hydrolysis. Cross-linking studies have established interaction between the GED and the N-terminal GTt)ase domait. (iurrenl work is directed towards identif.ving the mechanism by which the (;El) activates dynamin GTPase activity.

Original languageEnglish (US)
Pages (from-to)A1011
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Warnock, D. E., Muhlberg, S. B., Sever, S., & Schmid, S. L. (1997). Regulation of the dynamin GTPase cycle. FASEB Journal, 11(9), A1011.