Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Rab/Ypt small G proteins are essential for intracellular vesicle trafficking in mammals and yeast. The vesicle-docking process requires that Ypt proteins are located in the vesicle membrane. C-terminal geranylgeranyl anchors mediate the membrane attachment of these proteins. The Rab escort protein (REP) is essential for the recognition of Rab/Ypt small G proteins by geranylgeranyltransferase II (GGTase II) and for their delivery to acceptor membranes. What effect an alteration in the levels of prenylated Rab/Ypt proteins has on vesicle transport or other cellular processes is so far unknown. Here, we report the characterization of a yeast REP mutant, mrs6-2, in which reduced prenylation of Ypt proteins occurs even at the permissive temperature. A shift to the restrictive temperature does not alter exponential growth during the first 3 h. The amount of Sec4p, but not Ypt1p, bound to vesicle membranes is reduced 2.5 h after the shift compared with wild-type or mrs6-2 cells incubated at 25 degrees C. In addition, vesicles fail to be polarized towards the bud and small budded binucleate cells accumulate at this time point. Growth in 1 M sorbitol or overexpression of MLC1, encoding a myosin light chain able to bind the unconventional type V myosin Myo2, or of genes involved in cell wall maintenance, such as SLG1, GFA1 and LRE1, suppresses mrs6-2 thermosensitivity. Our data suggest that, at least at high temperature, a critical minimal level of Ypt protein prenylation is required for maintaining vesicle polarization.
Mol Microbiol 2000 Mar
PMID:Low levels of Ypt protein prenylation cause vesicle polarization defects and thermosensitive growth that can be suppressed by genes involved in cell wall maintenance. 1076 Jan 32

Isoprenylation is a posttranslational modification that transfers farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) to cysteine residues of a particular set of proteins, causing their localization to the plasma membrane and other cellular compartments and so rendering them biologically active. Such a modification process, catalyzed by protein prenyltransferase including farnesyltransferase (FT), geranylgeranyltransferase I (GGTI), and geranylgeranyltransferase II (GGTII), is required for the transforming activity of many oncogenic proteins, including some RAS family members. In the past three decades, prenyltransferase has been extensively studied as a promising cancer therapeutic target in vitro, in animal models, and in the clinic. Recently, a growing number of studies suggest that prenyltransferases and the substrates FPP and GGPP also play fundamental roles in nervous system development and brain disorders. However, a systemic review about the advances of prenyltransferases in the field of neuroscience is lacking so far. Herein, we give a brief introduction for the structure and distribution of GGTI and comprehensively updated the recent advances of GGTI in neuronal dendritogenesis/synaptogenesis and in learning/memory-related behavioral performance. More importantly, we discussed the involvement of GGTI and its substrate GGPP in neurodegenerative disorders, such as aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C. The role of FT-FPP and GGTII is mentioned as well to compare with GGTI in these physiological and pathological processes. We hope that this systematical review about what we know about GGTI research in the brain can stimulate further studies on the underlying mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders.
Mol Neurobiol 2016 12
PMID:The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain. 2666 64