Yueh Y G, Crain R C
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269-3125.
J Cell Biol. 1993 Nov;123(4):869-75. doi: 10.1083/jcb.123.4.869.
C. reinhardtii sheds its flagella in response to acidification. Previously, we showed correlations between pH shock, deflagellation, and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production, but 100% of cells deflagellated by 5 s, which was the earliest that Ins(1,4,5)P3 accumulation could be accurately measured by techniques available to us at that time (Quarmby, L. M., Y. G. Yueh, J. L. Cheshire, L. R. Keller, W. J. Snell, and R. C. Crain. J. Cell Biol. 1992. 116:737-744). To learn about the causal relationship between Ins(1,4,5)P3 accumulation and deflagellation, we extended these studies to early times using a continuous-flow rapid-quench device. Within 1 s of acidification to pH 4.3-4.5, 100% of cells deflagellated. A transient peak of Ins(1,4,5)P3 was observed 250-350 ms after pH shock, preceding deflagellation. Preincubation with 10 microM neomycin, which prevents hydrolysis of phosphatidylinositol 4,5-bisphosphate, inhibited both the transient production of Ins(1,4,5)P3 and the subsequent deflagellation. The nonspecific Ca2+ channel blockers La3+ and Cd2+ prevented flagellar excision induced by mastoparan without inhibiting rapid Ins(1,4,5)P3 production. Likewise, the Ins(1,4,5)P3-gated channel inhibitors ruthenium red and heparin blocked deflagellation in response to mastoparan. These studies were extended to mutants defective in flagellar excision. Fa-1, a mutant defective in flagellar structure, produced Ins(1,4,5)P3 but failed to deflagellate. These results support a model in which acid pH activates a putative cellular receptor leading to G-protein dependent activation of phospholipase C and accumulation of Ins(1,4,5)P3. These events are upstream of Ins(1,4,5)P3-dependent Ca2+ entry from the medium, and of deflagellation.
莱茵衣藻(Chlamydomonas reinhardtii)会因酸化作用而脱落鞭毛。此前,我们发现pH冲击、鞭毛脱落与肌醇1,4,5-三磷酸[Ins(1,4,5)P3]生成之间存在关联,但在5秒时100%的细胞都发生了鞭毛脱落,而这是当时我们所采用的技术能够准确测量Ins(1,4,5)P3积累的最早时间(Quarmby, L. M., Y. G. Yueh, J. L. Cheshire, L. R. Keller, W. J. Snell, and R. C. Crain. J. Cell Biol. 1992. 116:737 - 744)。为了了解Ins(1,4,5)P3积累与鞭毛脱落之间的因果关系,我们使用连续流动快速淬灭装置将这些研究扩展到了早期阶段。在酸化至pH 4.3 - 4.5后的1秒内,100%的细胞发生了鞭毛脱落。在pH冲击后250 - 350毫秒观察到Ins(1,4,5)P3出现一个短暂峰值,此峰值先于鞭毛脱落。用10微摩尔新霉素进行预孵育,新霉素可阻止磷脂酰肌醇4,5 - 二磷酸的水解,它既抑制了Ins(1,4,5)P3的短暂生成,也抑制了随后的鞭毛脱落。非特异性Ca2 +通道阻滞剂La3 +和Cd2 +可阻止mastoparan诱导的鞭毛切除,但不抑制Ins(1,4,5)P3的快速生成。同样,Ins(1,4,5)P3门控通道抑制剂钌红和肝素可阻止因mastoparan引起的鞭毛脱落。这些研究扩展到了鞭毛切除存在缺陷的突变体。Fa - 1是一种鞭毛结构存在缺陷的突变体,它能产生Ins(1,4,5)P3,但无法发生鞭毛脱落。这些结果支持了一个模型,即酸性pH激活一种假定的细胞受体,导致G蛋白依赖性激活磷脂酶C并积累Ins(1,4,5)P3。这些事件发生在Ins(1,4,5)P3依赖性Ca2 +从培养基进入细胞以及鞭毛脱落的上游。