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Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases.

ABSTRACT: Meristems require a myriad of intercellular signaling pathways for coordination of cell division within and between functional zones and clonal cell layers. This control of cell division ensures a constant availability of stem cells throughout the life span of the meristem while limiting overproliferation of meristematic cells and maintaining the meristem structure. We have undertaken a genetic screen to identify additional components of meristem signaling pathways. We identified pluripetala (plp) mutants based on their dramatically larger meristems and increased floral organ number. PLURIPETALA encodes the alpha-subunit shared between protein farnesyltransferase and protein geranylgeranyltransferase-I. plp mutants also have altered abscisic acid responses and overall much slower growth rate. plp is epistatic to mutations in the beta-subunit of farnesyltransferase and shows a synergistic interaction with clavata3 mutants. plp mutants lead to insights into the mechanism of meristem homeostasis and provide a unique in vivo system for studying the functional role of prenylation in eukaryotes.

SUBMITTER: Running MP

PROVIDER: S-EPMC419689 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature

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Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases.

Running Mark P MP Lavy Meirav M Sternberg Hasana H Galichet Arnaud A Gruissem Wilhelm W Hake Sarah S Ori Naomi N Yalovsky Shaul S

Proceedings of the National Academy of Sciences of the United States of America 20040505 20

Meristems require a myriad of intercellular signaling pathways for coordination of cell division within and between functional zones and clonal cell layers. This control of cell division ensures a constant availability of stem cells throughout the life span of the meristem while limiting overproliferation of meristematic cells and maintaining the meristem structure. We have undertaken a genetic screen to identify additional components of meristem signaling pathways. We identified pluripetala (pl ...[more]

PMID: 15128936

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Project description:BackgroundThe CAAX-prenyltransferases farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) are heterodimers with a common α- (FTα) and unique β-subunits. Recently, α-subunits of species (e.g., human) that harbour an N-terminal proline-rich region (PRR) showed different dimerization behaviours than α-subunits without PRR (e.g., yeast). However, the specific function of the PRR has not been elucidated so far.MethodsTo determine whether the PRR is a conserved motif throughout eukaryotes, we performed phylogenetics. Elucidating the impact of the PRR on enzyme properties, we cloned human as well as rat PRR deficient FTα, expressed them heterologously and compared protein-protein interaction by pull-down as well as crosslinking experiments. Substrate binding, enzyme activity and sensitivity towards common FTase inhibitors of full length and PRR-deletion α-subunits and their physiological partners was determined by continuous fluorescence assays.ResultsThe PRR is highly conserved in mammals, with an exception for marsupials harbouring a poly-alanine region instead. The PRR shows similarities to canonical SH3-binding domains and to profilin-binding domains. Independent of the PRR, the α-subunits were able to dimerize with the different physiological β-subunits in in vitro as well as in yeast two-hybrid experiments. FTase and GGTase I with truncated FTα were active. The KM values for both substrates are in the single-digit µM range and show no significant differences between enzymes with full length and PRR deficient α-subunits within the species.ConclusionsOur data demonstrate that an N-terminal PRR of FTα is highly conserved in mammals. We could show that the activity and inhibitability is not influenced by the truncation of the N-terminal region. Nevertheless, this region shows common binding motifs for other proteins involved in cell-signalling, trafficking and phosphorylation, suggesting that this PRR might have other or additional functions in mammals. Our results provide new starting points due to the relevant but only partly understood role of FTα in eukaryotic FTase and GGTase I. Video Abstract.

Project description:BackgroundA fecal test followed by diagnostic colonoscopy for a positive result is a widely endorsed screening strategy for colorectal cancer (CRC). However, the relationship between the time delay from the positive test to the follow-up colonoscopy and CRC mortality has not been established.MethodsFrom a population-based screening program, we identified CRC patients newly diagnosed from 2005 through 2015 by a positive fecal occult test followed by a colonoscopy. The primary outcome measure was CRC-specific mortality according to four categories for the time elapsed between the positive result and the subsequent colonoscopy.ResultsThe 1749 patients underwent colonoscopies within 0-3 months (n = 981, 56.1%), 4-6 months (n = 307, 17.5%), 7-12 months (n = 157, 9.0%), and later than 12 months (n = 304, 17.4%). CRC-specific deaths according to exposure groups were: 13.8% (135 of 981) for 0-3 months, 10.7% (33 of 307) for 4-6 months (crude hazards ratio [HR] = 0.74, 95% confidence interval [CI] = 0.51 to 1.14), 11.5% (18 of 157) for 7-12 months (crude HR = 0.83, 95% CI = 0.51 to 1.42), and 22.7% (69 of 304) for longer than 12 months (crude HR = 1.40, 95% CI = 1.04 to 1.90). The only variable that was associated with mortality risk was the number of positive slides (P = .003). High positivity was twice the value in the 0-3 as the longer-than-12 months group: 51.9% vs 25.0% and similar for the 4-6 and 7-12 months groups (38.1% and 36.5%), respectively. The adjusted HRs for CRC mortality were 0.81 (95% CI = 0.55 to 1.19); 0.83 (95% CI = 0.50 to 1.41), and 1.53 (95% CI = 1.13 to 2.12, P = .006) for the 4-12, 7-12, and longer-than-12-months groups, respectively, compared with the shortest delay group.ConclusionsAmong screen-diagnosed CRC patients, performance of colonoscopy more than 12 months after the initial positive fecal occult blood test was associated with more advanced disease and higher mortality due to CRC.

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Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases.

Publications

Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases.

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