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A list by Prachee Avasthi Recommended Reading
See what researchers at Prachee Avasthi’s lab are reading to discover some interesting new work.
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Diffusive lensing as a mechanism of intracellular transport and compartmentalization
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
With diffusion being inversely correlated with viscosity, this super interesting modeling study got me thinking about intracellular transport based on viscosity gradients (viscophoresis) or non-homogeneous viscosity within a cell. They call this “diffusive lensing” and speculate it drives a lot of biological processes at the meso scale.
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Functionally conserved Pkd2, mutated in autosomal dominant polycystic kidney disease, localizes to the endoplasmic reticulum and regulates cytoplasmic calcium homeostasis in fission yeast
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
Pkd2 mutations result in autosomal dominant polycystic kidney disease (PKD), characterized as a ciliopathy due to the ciliary localization and impact of protein dysfunction, though the relationship with cilium structure and function for PKD remains murky given cilium disruption on a pkd2 mutant background can ameliorate cystic phenotypes. Studying functions of this protein OUTSIDE cilia via a model that lacks cilia entirely (yeast) is sure to be informative in teasing apart these complex interdependencies
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Comparative analysis of actin visualization by genetically encoded probes in cultured neurons
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
There are few things I enjoy more than a comparative analysis of actin probes. Another of my all time favorites is this: https://www.tandfonline.com/doi/full/10.1080/19490992.2014.1047714
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A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
This is an unbelievably interesting study on mictotubule and MTOC behavior during phagocytosis of apoptotic cells by microglia during zebrafish development. Check out the relative contributions of actin and mictotubules in branch mediated engulfment in figures 2E and F and the role of centrosome movement into these branches in figures 4 and 5 for successful phagocytosis, which can explain the one at a time behavior typically seen in these cells. This is tested further by artificially increasing centrosome number by centrin 4 over-expression and concurrent phagocytic events. They even look at vesicular trafficking and mechanisms of centrosome reorientation. Honestly this feels like several papers worth of work.
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ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
Understanding ARPC5 and its isoforms, a component of the branched actin nucleating Arp2/3 complex is a fascinating topic. They find here (in addition to effects on ARPC1 and ENA/VASP) that knocking out both isoforms eliminates lamellipodia (the branched actin sheets at the leading edge of migrating cells). Some fun facts: Chlamydomonas cells don’t seem to have an ARPC5 (though we are working to confirm this), nor lamallipodia AND ARPC5 is the target of a microRNA miR-133a that is up-regulated in many human cancers. There are lots of interesting migration/metastasis related implications for ARPC5 regulation.
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Beyond sequence similarity: cross-phyla protein annotation by structural prediction and alignment
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
If you’ve ever worked in a model or non-model system, finding putative orthologs can be difficult given low sequence homology. Structure is much more well conserved across taxa and given recent advancements in structural prediction made possible by AlphaFold2 and methods built upon it (here ColabFold), structural homology based functional annotation of proteins across phyla is easier than ever!
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Condensate functionalization with motors directs their nucleation in space and allows manipulating RNA localization
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
A useful tool that can be used for testing functions of localized mRNAs and consequences of disrupting their targeting. Condensate scaffolds and chemically inducible condensates are engineered to test effects of motor proteins on mRNA/RNP localization. The scaffolds move based on typical motor direction (minus end microtubule motors were much faster for transport of non-functionalized condensate scaffolds, possibly due to availability of scaffolds and molecular crowding in different parts of the cell). Chemically inducible condensate formation on motors was achieved and mRNA recruitment to condensates successfully disrupted endogenous localization.
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APC couples neuronal mRNAs to multiple kinesins, EB1 and shrinking microtubule ends for bidirectional mRNA motility
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
I somehow missed this the first time but this [revision] is unbelievably cool. APC can bind the 3’UTR of RNAs as an adaptor for kinesin-1 and -2 (the ciliary kinesin!) for trafficking on mictotubules. This is shown via in vitro reconstitution experiments and it appears that these complexes track plus ends in an EB1 dependent manner but can stay associated in shrinking MTs in an EB1-independent manner.
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Multifunctional fluorophores for live-cell imaging and affinity capture of proteins
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
This is awesome. Multifunctional cell permeable ligands (fluorophore+biotin) that can be used with haloTag fusion proteins for both visualization and affinity capture!
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Large-scale identification of phospho-modulated motif-based protein-protein interactions
This article's authorsAnnotation by Prachee Avasthi Recommended Reading
Omg this is so cool! A peptide phage display approach to screen for functionally relevant phospho-sites. They do some structural, evolutionary and other analyses to prioritize phosphorites within intrinsically disordered regions containing short linear motifs that often mediate phospho-dependent interactions. They then screen through expression/binding to uncover novel interactions mediated by phosphorylation that they are able to validate in many instances. Neat approach and a wealth of data to be mined. Check out the supplemental tables.