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Regulation of differentiation in slime mold cells

粘菌细胞分化的调节

基本信息

批准号：
06044234
负责人：
TAKEUCHI Ikuo
金额：
$ 3.46万
依托单位：
Okazaki National Research Institutes
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06044234/
关键词：
cell differentiation gene expression cell growth cell cycle signal transduction cellular slime mold パターン形成

项目摘要

In the development of cellular slime molds, cells aggregate to form a tissue, in which two types of cells (prestalk and prespore) differentiate in the anterior and the posterior parts, respectively.To elucidate regulatory mechanisms of differentiation, we made the following studies.1.Relation of cell growth and differentiationWhether cells differentiate into either prestalk or prespore cells in the tissue is related to the cell cycle phase at the time of starvation.Putative shift (PS) point from growth to differentiation was determined and genes specifically expressed at the point were examined.Three kinds of genes (Quit 1,2,3) were identified.The Quit gene encodes a cAMP receptor, CAR1 and the Quit2 a new type of calcium-binding protein (CAF-1).2.Mechanism of stalk cell-inducing factorCells secrete during development a factor inducing stalk cell differentiation (STIF).The fact that STIF is replaced by 8-bromo-cAMP suggests that STIF acts through protein kinase A (PKA).This possibility was verified, as cells transformed with a dominant negative inhibitor of PKA was incapable of stalk cell formation.STIF activates stalk-specific ecmB gene, but not ecmA gene.The upstream region of ecmB promoter where STTF acts was identified by using cells transformed with various deleted genes.3.Role of MAP-kinase in signal transduction.Analysis of an aggregateless mutant indicated a MAP-kinase, ERK2 gene has an important role in chemotaxis of cells.ERK2 was activated by extracellular cAMP through membrane receptors, CAR1 and CAR3 and eventually activates adenylate cyclase (AC), without involving heterotrimetric G-proteins.Activation of AC results in an increase in cellular cAMP which in turn inactivates ERK2.Activation of ERK2 is essential for cell growth during the vegetative phase, which is brought about by folic acid and strongly depends on the G proteins.

在细胞黏菌的发育过程中，细胞聚集形成一个组织，其中有两种类型的细胞（前柄和前孢子）分别在前部和后部分化。为了阐明分化的调节机制，本研究主要做了以下几个方面的工作：1.细胞生长与分化的关系细胞在组织中分化为前柄细胞或前孢子细胞与细胞周期时相有关。测定了从生长到分化的假定转变点（PS），并检测了在该点特异性表达的基因。Quit基因编码cAMP受体，CAR 1和Quit 2是一种新型的钙结合蛋白（CAF-1）。诱导因子细胞在发育过程中分泌一种诱导柄细胞分化的因子（STIF），STIF被8-溴-cAMP所取代，说明STIF通过蛋白激酶A（PKA）起作用，证实了这一可能性，STIF激活茎特异性的ecmB基因，但不激活ecmA基因。用各种缺失基因转化的细胞鉴定了STTF作用的ecmB启动子上游区域。3. MAP激酶在信号转导中的作用。对一个无聚集体突变体的分析表明，ERK 2基因在细胞趋化性中起重要作用，细胞外cAMP通过膜受体CAR 1和CAR 3激活ERK 2，最终激活腺苷酸环化酶（AC），而不涉及异三聚体G蛋白。AC的激活导致细胞内cAMP增加，从而使ERK 2失活。ERK 2的激活对细胞生长至关重要，这是由叶酸引起的，并且强烈依赖于G蛋白。