Insulin biomolecular condensate formed in ionic microenvironment modulates the structural properties of pristine and magnetic cellulosic nanomaterials

Karmakar, Srijeeb; Ghosh, Tabli; Sankhla, Arjun; Bhattacharjee, Sayan Kumar; Katiyar, Vimal

doi:10.1016/j.molliq.2022.119580

Cited by 2 publications

(2 citation statements)

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“…The first key finding was that, under conditions that mimic those along the secretory pathway, the three proteins self‐associate and form nanocondensates. At the time of this investigation, the capacity of insulin to assemble and populate nanocondensates at neutral pH in vitro was well known (Dodson and Steiner, 1998 ; Pekar and Frank, 1972 ; Nielsen et al, 2001 ; Attri et al, 2010 ; Wijesekara et al, 2010 ; Landreh et al, 2012 ; Xu et al, 2012 ; Nilsson, 2016 ; Dzianová et al, 2020 ; Kaissaratos et al, 2021 ; Karmakar et al, 2022 ; Silva‐Jr et al, 2022 ; Jonassen et al, 2012 ), but proinsulin had been much less studied in this regard (Pekar and Frank, 1972 ). On the other hand, in previous works, we had presented evidence of the self‐condensation of RESP18HD (Sosa et al, 2016 ; Toledo et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Common SG residents, such as islet amyloid polypeptide (IAPP), and CGA and CGB have been found to undergo in vivo and/or in vitro conformational transitions that result in biomolecular condensation (Parchure et al, 2022 ; Zhao et al, 2009 ; Horvath and Wittung‐Stafshede, 2016 ). Likewise, under a variety of conditions, in vivo and in vitro, insulin forms multimers and nano‐ and micro‐condensates with different material properties: liquid condensation, amorphous aggregation, crystallization, and fibrillation (Dodson and Steiner, 1998 ; Lemaire et al, 2009 ; Nielsen et al, 2001 ; Attri et al, 2010 ; Wijesekara et al, 2010 ; Landreh et al, 2012 ; Xu et al, 2012 ; Nilsson, 2016 ; Dzianová et al, 2020 ; Kaissaratos et al, 2021 ; Karmakar et al, 2022 ; Silva‐Jr et al, 2022 ; Asai et al, 2022 ). CGB undergoes liquid–liquid phase separation under conditions mimicking those present in the TGN, where proinsulin was found organized as dynamic puncta and co‐localized with PC2.…”

Section: Introductionmentioning

confidence: 99%

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Condensation of the β‐cell secretory granule luminal cargoes pro/insulin and ICA512 RESP18 homology domain

et al. 2023

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ICA512/PTPRN is a receptor tyrosine‐like phosphatase implicated in the biogenesis and turnover of the insulin secretory granules (SGs) in pancreatic islet beta cells. Previously we found biophysical evidence that its luminal RESP18 homology domain (RESP18HD) forms a biomolecular condensate and interacts with insulin in vitro at close‐to‐neutral pH, that is, in conditions resembling those present in the early secretory pathway. Here we provide further evidence for the relevance of these findings by showing that at pH 6.8 RESP18HD interacts also with proinsulin—the physiological insulin precursor found in the early secretory pathway and the major luminal cargo of β‐cell nascent SGs. Our light scattering analyses indicate that RESP18HD and proinsulin, but also insulin, populate nanocondensates ranging in size from 15 to 300 nm and 10e2 to 10e6 molecules. Co‐condensation of RESP18HD with proinsulin/insulin transforms the initial nanocondensates into microcondensates (size >1 μm). The intrinsic tendency of proinsulin to self‐condensate implies that, in the ER, a chaperoning mechanism must arrest its spontaneous intermolecular condensation to allow for proper intramolecular folding. These data further suggest that proinsulin is an early driver of insulin SG biogenesis, in a process in which its co‐condensation with RESP18HD participates in their phase separation from other secretory proteins in transit through the same compartments but destined to other routes. Through the cytosolic tail of ICA512, proinsulin co‐condensation with RESP18HD may further orchestrate the recruitment of cytosolic factors involved in membrane budding and fission of transport vesicles and nascent SGs.

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