Exocytotic fusion pore under stress.

IF 4.1 Q2 CELL BIOLOGY
Helena Haque Chowdhury, Robert Zorec
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引用次数: 0

Abstract

Exocytosis is a universal process of eukaryotic cells, consisting of fusion between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a channel through which vesicle cargo exits into the extracellular space. In 1986, Rand and Parsegian proposed several stages to explain the nature of membrane fusion. Following stimulation, it starts with focused stress destabilization of membranes in contact, followed by the coalescence of two membrane surfaces. In the next fraction of a millisecond, restabilization of fused membranes is considered to occur to maintain the cell's integrity. This view predicted that once a fusion pore is formed, it must widen abruptly, irreversibly and fully, whereby the vesicle membrane completely integrates with and collapses into the plasma membrane (full fusion exocytosis). However, recent experimental evidence has revealed that once the fusion pore opens, it may also reversibly close (transient or kiss-and-run exocytosis). Here, we present a historical perspective on understanding the mechanisms that initiate the membrane merger and fusion pore formation. Next, post-fusion mechanisms that regulate fusion pore stability are considered, reflecting the state in which the forces of widening and constriction of fusion pores are balanced. Although the mechanisms generating these forces are unclear, they may involve lipids and proteins, including SNAREs, which play a role not only in the pre-fusion but also post-fusion stages of exocytosis. How molecules stabilize the fusion pore in the open state is key for a better understanding of fusion pore physiology in health and disease.

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压力下的外吞融合孔。
外吞是真核细胞的一个普遍过程,包括囊泡和质膜之间的融合,从而形成一个融合孔,囊泡货物通过这个通道进入细胞外空间。1986 年,Rand 和 Parsegian 提出了几个阶段来解释膜融合的本质。在受到刺激后,首先是接触膜的聚焦应力不稳定,然后是两个膜表面的凝聚。在接下来的几毫秒内,融合的膜会重新稳定,以保持细胞的完整性。这种观点认为,融合孔一旦形成,就必须突然、不可逆地完全扩大,囊泡膜由此完全与质膜结合并塌陷到质膜中(完全融合外渗)。然而,最近的实验证据表明,一旦融合孔打开,它也可能可逆地关闭(瞬时或亲吻-运行外渗)。在此,我们将从历史的角度来了解启动膜合并和融合孔形成的机制。接下来,我们考虑了调节融合孔稳定性的融合后机制,它反映了融合孔扩大和收缩的力量达到平衡的状态。虽然这些力量的产生机制尚不清楚,但可能涉及脂质和蛋白质,包括 SNAREs,它们不仅在外渗的融合前阶段发挥作用,而且在融合后阶段也发挥作用。分子如何将融合孔稳定在开放状态,是更好地了解融合孔在健康和疾病中的生理作用的关键。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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