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Study of cellular responses to membrane damages

Abstract : The integrity of cell membranes is essential for their survival and for the proper functioning of the cell. However, these membranes are constantly exposed to damage. The first part of this research concerns the study of plasma membrane repair following exposure to physical assaults and chemical or biochemical toxins. We describe a new mechanism for plasma membrane repair that involves the complex III of the ESCRT (endosomal sorting complex required for transport) machinery. Our observations suggest that the ESCRT machinery may be involved in removing damaged portions of the plasma membrane by budding. We believe that our results represent a valuable contribution to the field of ESCRTs. The second part of this study focuses on the cellular response to physical (laser) damage or chemical (by chemical cross-linking) damage of trafficking organelles. We demonstrate the involvement of the mechanisms of autophagy in response to endosome and Golgi apparatus damage. This response includes the rapid recruitment of the protein LC3 (main protein detectable on the membranes of mature autophagosomes). We have also shown the involvement of ubiquitination and the rapid recruitment of proteins p62 and NBR1, which are proteins that can bind both ubiquitin and LC3. The observed mechanism has much in common with other mechanisms of selective autophagy but reveals peculiarities such as the direct recruitment of LC3 on the membranes of damaged Golgi apparatus. Thus, our research includes the study of two cellular mechanisms of response to membrane damage that highlight the existence of mechanisms for systematic monitoring of homeostasis of organelles and the plasma membrane. These mechanisms are adapted to the specific nature of the damaged membranes. We show that damage to certain trafficking organelles (endosomes and the Golgi apparatus) triggers the response machinery of autophagy whilst damage to the plasma membrane induces a new repair mechanism involving the machinery of ESCRTs
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Submitted on : Friday, June 7, 2013 - 11:51:59 AM
Last modification on : Tuesday, November 16, 2021 - 4:36:19 AM
Long-term archiving on: : Tuesday, April 4, 2017 - 6:10:18 PM

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  • HAL Id : tel-00831574, version 1

Citation

Ana Joaquina Jimenez. Study of cellular responses to membrane damages. Cellular Biology. Université Pierre et Marie Curie - Paris VI, 2012. English. ⟨NNT : 2012PAO66405⟩. ⟨tel-00831574⟩

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