Exp Mol Med.  2001 Dec;33(4):220-225.

The proteins of synaptic vesicle membranes are affected during ageing of rat brain

• Lee SR
• Kim AR
• Kim JS
• Kim JB
• Lee JY
• Lee YL
• Choe M
• Park JB

Abstract

Low molecular weight GTP-binding proteins are molecular switches that are believed to play pivotal roles in cell growth, differentiation, cytoskeletal organization, and vesicular trafficking. Rab proteins are key players in the regulation of vesicular transport, while Rho family members control actin-dependent cell functions, i.e. the regulation of cytoskeletal organization in response to extracelluar growth factors and in dendritic neuron development. In this study, we have examined the regulation of small GTP-binding proteins that are implicated in neurosecretion and differentiation of neuron during ageing processes. Comparison of small GTP-binding proteins from the synaptosome and crude synaptic vesicles (LP2 membranes) of 2 months and 20 months old rat brain respectively showed no difference in the level of Rab family proteins (Rab3A and Rab5A). However, Rho family proteins such as RhoA and Cdc42 were elevated in LP2 membranes of the aged brain. The dissociation of Rab3A by Ca2+/calmodulin (CaM) from SV membranes was not changed during aging. Ca2+/CaM stimulated phosphorylation of the 22 and 55-kDa proteins in SV membranes from the aged rat brain, and inhibited phosporylation of 30-kDa proteins. GTPgammaS inhibited phosphorylation of the 100-kDa proteins and stimulated phosphorylation of the 70 kDa in LP2 membranes from both the young and aged rat brains, whereas GDPbetaS caused just the opposite reaction. These results suggest that protein phosphorylation and regulation of Rho family GTPases in rat brain appears to be altered during ageing processes.

Keyword

Small GTP-binding proteins; Rab3A; Rab5; Cdc42; RhoA; guanine nucleotides; Phosphorylation; Synaptic vesicle

MeSH Terms

*Aging
Animal
Brain/metabolism
Calcium/pharmacology
Cattle
Comparative Study
GTP-Binding Proteins/*metabolism
Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
Molecular Weight
Phosphorylation/drug effects
Rats
Rats, Sprague-Dawley
Synaptic Membranes/*metabolism
Synaptosomes/*metabolism
cdc42 GTP-Binding Protein/biosynthesis/metabolism
rab3A GTP-Binding Protein/metabolism
rab5 GTP-Binding Proteins/metabolism
rhoA GTP-Binding Protein/biosynthesis/metabolism