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Kumari, A.

Publications and source records attributed to Kumari, A..

2 recordsLinked to original sources

Actomyosin-driven force patterning controls endocytosis at the immune synapse

An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules [1]. Although [2], how forces organize and mechanics has been shown to play an important role in this process impact on synapse function is unknown. We found that mechanical forces are spatio-temporally patterned at the immune synapse: global contractile forces are observed at the synapse periphery and local point-like forces are detected at its centre. The global contractile forces result from a pulsatile centripetal actomyosin flow that leads to formation of F-actin protrusions from which the central point like forces emerge. Noticeably, these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis. Accordingly, deletion of the myosin IIA gene leads to impaired B cell responses. The interplay between global and local forces governed by the actomyosin cytoskeleton therefore controls the endocytic function of the immune synapse and might constitute a more general mechanism in the physical regulation of cell-cell interactions.

cell biology

An RNAi screen in human cell lines reveals conserved DNA damage repair pathways that mitigate formaldehyde sensitivity

Formaldehyde is a ubiquitous DNA damaging agent, with human exposures occuring from both exogenous and endogenous sources. Formaldehyde can also form DNA-protein crosslinks and is representative of other such DNA damaging agents including ionizing radiation, metals, aldehydes, chemotherapeutics, and cigarette smoke. In order to identify genetic determinants of cell proliferation in response to continuous formaldehyde exposure, we quantified cell proliferation after siRNA-depletion of a comprehensive array of over 300 genes representing all of the major DNA damage response pathways. Three unrelated human cell lines (SW480, U-2 OS and GM00639) were used to identify common or cell line-specific mechanisms. Four cellular pathways were determined to mitigate formaldehyde toxicity in all three cell lines: homologous recombination, double-strand break repair, ionizing radiation response, and DNA replication. Differences between cell lines were further investigated by using exome sequencing and Cancer Cell Line Encyclopedia genomic data. Our results reveal major genetic determinants of formaldehyde toxicity in human cells and provide evidence for the conservation of these formaldehyde responses between human and budding yeast.

cell biology