Lane Jon D, Allan Victoria J, Woodman Philip G
University of Bristol, Department of Biochemistry, School of Medicine, University Walk, Bristol, BS8 1TD, UK.
J Cell Sci. 2005 Sep 1;118(Pt 17):4059-71. doi: 10.1242/jcs.02529.
Plasma membrane blebbing is a defining characteristic of apoptosis, but its significance is not understood. Using live-cell imaging we have identified two phases of apoptotic blebbing. The early phase is restricted to adherent cells, and is prevented by the Rho-activated kinase inhibitor Y27632. The late phase is partially resistant to Y27632, and generates morphologically distinct membrane protrusions that are likely precursors to apoptotic bodies. Late blebbing is observed in all apoptotic cells tested. It occurs at a fixed period before phosphatidyl serine exposure, indicating that it is a universal and important feature of apoptosis. Late blebs contain a cortical layer of endoplasmic reticulum that often surrounds condensed chromatin, while other organelles are excluded. The appearance in some apoptotic cells of partially formed sheets of endoplasmic reticulum suggest that these cortical layers are newly formed by the remodelling of the endoplasmic reticulum of interphase cells. Formation of endoplasmic reticulum and chromatin-containing blebs requires both actin and microtubules, and is prevented by the caspase-6 inhibitor zVEID.fmk.
质膜起泡是细胞凋亡的一个决定性特征，但其意义尚不清楚。通过活细胞成像，我们确定了凋亡性起泡的两个阶段。早期阶段仅限于贴壁细胞，并可被Rho激活激酶抑制剂Y27632阻止。晚期阶段对Y27632有部分抗性，并产生形态上不同的膜突起，这些突起可能是凋亡小体的前体。在所有测试的凋亡细胞中都观察到晚期起泡。它发生在磷脂酰丝氨酸暴露之前的固定时期，表明它是细胞凋亡的一个普遍且重要的特征。晚期泡包含一层内质网皮质层，该层通常围绕着凝聚的染色质，而其他细胞器则被排除在外。在一些凋亡细胞中出现的部分形成的内质网片层表明，这些皮质层是由间期细胞内质网的重塑新形成的。内质网和含染色质泡的形成需要肌动蛋白和微管，并且可被半胱天冬酶-6抑制剂zVEID.fmk阻止。
