Essential role of small GTPase Rac1 during limb development

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S50-S51
Author(s):  
D. Suzuki ◽  
A. Yamada ◽  
T. Amano ◽  
A. Kimura ◽  
R. Yasuhara ◽  
...  
2001 ◽  
Vol 98 (2) ◽  
pp. 759-764 ◽  
Author(s):  
E. Ono ◽  
H. L. Wong ◽  
T. Kawasaki ◽  
M. Hasegawa ◽  
O. Kodama ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27879 ◽  
Author(s):  
Fang Xia ◽  
Takehiko Dohi ◽  
Nina M. Martin ◽  
Christopher M. Raskett ◽  
Qin Liu ◽  
...  

Reproduction ◽  
2014 ◽  
Vol 147 (5) ◽  
pp. 615-625 ◽  
Author(s):  
M D Baker ◽  
M Ezzati ◽  
G M Aloisio ◽  
E D Tarnawa ◽  
I Cuevas ◽  
...  

The process of germ cell development is under the tight control of various signaling pathways, among which the PI3K-Akt-mTOR pathway is of critical importance. Previous studies have demonstrated sex-specific roles for several components of this pathway. In the current study, we aimed to evaluate the role of Rheb, a member of the small GTPase superfamily and a critical component for mTORC1 activation, in male and female gametogenesis. The function of Rheb in development and the nervous system has been extensively studied, but little is known about its role in the germ line. We have exploited genetic approaches in the mouse to study the role of Rheb in the germ line and have identified an essential role in spermatogenesis. Conditional knockout (cKO) of Rheb in the male germ line resulted in severe oligoasthenoteratozoospermia and male sterility. More detailed phenotypic analyses uncovered an age-dependent meiotic progression defect combined with subsequent abnormalities in spermiogenesis as evidenced by abnormal sperm morphology. In the female, however, germ-cell specific inactivation of Rheb was not associated with any discernible abnormality; these cKO mice were fertile with morphologically unremarkable ovaries, normal primordial follicle formation, and subsequent follicle maturation. The absence of an abnormal ovarian phenotype is striking given previous studies demonstrating a critical role for the mTORC1 pathway in the maintenance of primordial follicle pool. In conclusion, our findings demonstrate an essential role of Rheb in diverse aspects of spermatogenesis but suggest the existence of functionally redundant factors that can compensate for Rheb deficiency within oocytes.


2009 ◽  
Vol 335 (2) ◽  
pp. 396-406 ◽  
Author(s):  
Dai Suzuki ◽  
Atsushi Yamada ◽  
Takanori Amano ◽  
Rika Yasuhara ◽  
Ayako Kimura ◽  
...  

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
N Lange ◽  
S Sieber ◽  
A Erhardt ◽  
G Sass ◽  
HJ Kreienkamp ◽  
...  

1995 ◽  
Vol 74 (05) ◽  
pp. 1323-1328 ◽  
Author(s):  
Dominique Lasne ◽  
José Donato ◽  
Hervé Falet ◽  
Francine Rendu

SummarySynthetic peptides (TRAP or Thrombin Receptor Activating Peptide) corresponding to at least the first five aminoacids of the new N-terminal tail generated after thrombin proteolysis of its receptor are effective to mimic thrombin. We have studied two different TRAPs (SFLLR, and SFLLRN) in their effectiveness to induce the different platelet responses in comparison with thrombin. Using Indo-1/AM- labelled platelets, the maximum rise in cytoplasmic ionized calcium was lower with TRAPs than with thrombin. At threshold concentrations allowing maximal aggregation (50 μM SFLLR, 5 μM SFLLRN and 1 nM thrombin) the TRAPs-induced release reaction was about the same level as with thrombin, except when external calcium was removed by addition of 1 mM EDTA. In these conditions, the dense granule release induced by TRAPs was reduced by over 60%, that of lysosome release by 75%, compared to only 15% of reduction in the presence of thrombin. Thus calcium influx was more important for TRAPs-induced release than for thrombin-induced release. At strong concentrations giving maximal aggregation and release in the absence of secondary mediators (by pretreatment with ADP scavengers plus aspirin), SFLLRN mobilized less calcium, with a fast return towards the basal level and induced smaller lysosome release than did thrombin. The results further demonstrate the essential role of external calcium in triggering sustained and full platelet responses, and emphasize the major difference between TRAP and thrombin in mobilizing [Ca2+]j. Thus, apart from the proteolysis of the seven transmembrane receptor, another thrombin binding site or thrombin receptor interaction is required to obtain full and complete responses.


1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.


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