Biology subjects

Basu, M. K.

Publications and source records attributed to Basu, M. K..

3 recordsLinked to original sources

bioRxiv2024

Time-resolved function of cell polarity kinases PRKCZ and PRKCI in CNS myelination

The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC - PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz - are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development.

developmental biology↗

bioRxiv2020

IL-4-induced hysteresis in naive T cell activation

Naive T cells are generally considered to be a homogeneous population, but for their unique T cell receptors (TCRs). Naive T cells are activated within a specific cytokine milieu upon interaction with antigen-presenting cells through cognate TCR::MHC-peptide interaction and co-stimulation. Here we demonstrate that naive T cells are transcriptionally heterogeneous, and that the relative proportions of transcriptionally distinct naive T cell subpopulations are modified by immune responses, such as during helminth infection. Not only are cognate naive T cells activated during an immune response, but the cytokine produced - such as IL-4 during helminth infection - changes the transcriptome of bystander naive T cells. Such changes in gene expression and population level heterogeneity in bystander naive T cells result in altered responses to a concurrent immune challenge, for instance, hypo-responsiveness to vaccination. Thus, naive T cell activation is not the result of a singular temporal event, but is characterized by hysteresis. Our studies suggest that antigen-agnostic, cytokine-dependent naive T cell conditioning and resulting hysteresis is a mechanism that integrates input signals from concurrent infections for the regulation of the overall magnitude of the immune response.

immunology↗

bioRxiv2019

Mito-SinCe2 Approach to Quantify Relationships between Mitochondrial Dynamics and Energetics status

Mitochondrial dynamics primarily refers to the opposing fission and fusion events between individual mitochondria, which maintains steady-state mitochondrial morphology in cells. The details of the bidirectional relationship between mitochondrial dynamics and energetics are unclear as the methods to integrate these mitochondrial aspects are lacking. To study the quantitative relationship between mitochondrial dynamics (fission, fusion, matrix continuity and diameter) and energetics (ATP and redox), we have developed and validated an analytical approach, mito-SinCe2. Application of this approach led to the hypothesis that mitochondria-dependent ovarian tumor initiating cells interconvert between 3 states with distinct relationships between mitochondrial energetics and dynamics. Interestingly, fusion and ATP increase linearly with each other only once a certain level of fusion is attained. Moreover, mitochondrial dynamics status changes linearly either with ATP or with redox, but not simultaneously with both. Furthermore, mito-SinCe2 analyses can potentially predict new quantitative features of the opposing fission vs. fusion relationship and classify cells into functional classes based on their mito-SinCe2 states.

cell biology↗