MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.
J Cell Sci. 2010 Oct 1;123(Pt 19):3226-34. doi: 10.1242/jcs.072876. Epub 2010 Aug 31.
We investigated the link between cell movement and plasma membrane recycling using a fast-acting, temperature-sensitive mutant of the Dictyostelium SecA exocytic protein. Strikingly, most mutant cells become almost paralysed within minutes at the restrictive temperature. However, they can still sense cyclic-AMP (cAMP) gradients and polymerise actin up-gradient, but form only abortive pseudopodia, which cannot expand. They also relay a cAMP signal normally, suggesting that cAMP is released by a non-exocytic mechanism. To investigate why SecA is required for motility, we examined membrane trafficking in the mutant. Plasma membrane circulation is rapidly inhibited at the restrictive temperature and the cells acquire a prominent vesicle. Organelle-specific markers show that this is an undischarged contractile vacuole, and we found the cells are correspondingly osmo-sensitive. Electron microscopy shows that many smaller vesicles, probably originating from the plasma membrane, also accumulate at the restrictive temperature. Consistent with this, the surface area of mutant cells shrinks. We suggest that SecA mutant cells cannot move at the restrictive temperature because their block in exocytosis results in a net uptake of plasma membrane, reducing its area, and so restricting pseudopodial expansion. This demonstrates the importance of proper surface area regulation in cell movement.
我们使用快速作用、温度敏感的 Dictyostelium SecA 胞吐蛋白突变体研究了细胞运动和质膜回收之间的联系。引人注目的是,大多数突变细胞在限制温度下几分钟内几乎完全瘫痪。然而,它们仍然可以感知环腺苷酸 (cAMP) 梯度并向上游聚合肌动蛋白,但只能形成无法扩展的短暂伪足。它们还能正常传递 cAMP 信号,表明 cAMP 通过非胞吐机制释放。为了研究 SecA 为何对运动至关重要,我们研究了突变体中的膜运输。在限制温度下,质膜循环迅速被抑制,细胞获得一个明显的囊泡。细胞器特异性标记表明这是一个未排出的收缩泡,并且我们发现细胞相应地对渗透压敏感。电子显微镜显示,许多较小的囊泡,可能来自质膜,也在限制温度下积累。与此一致的是,突变细胞的表面积收缩。我们认为,SecA 突变细胞在限制温度下不能移动,因为它们在胞吐作用中的阻断导致质膜的净摄取,从而减少其面积,并限制伪足的扩展。这表明适当的表面积调节对细胞运动至关重要。