Publications by authors named "Sreeja V Nair"

5 Publications

  • Page 1 of 1

Naturally occurring and tumor-associated variants of RNF167 promote lysosomal exocytosis and plasma membrane resealing.

J Cell Sci 2020 06 11;133(11). Epub 2020 Jun 11.

School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Thiruvananthapuram 695551, Kerala, India

Lysosomal exocytosis and resealing of damaged plasma membrane are essential for cellular homeostasis and tumor invasion. However, very little is known of the molecular machinery that regulates these physiological processes. Moreover, no mutations in any of the known regulators of lysosomal exocytosis in primary tumors of patients have been characterized. Here we demonstrate that RNF167-a, a lysosomal-associated ubiquitin ligase, negatively regulates lysosomal exocytosis by inducing perinuclear clustering of lysosomes. Importantly, we also characterized a set of novel natural mutations in RNF167-a, which are commonly found in diverse tumor types. We found that RNF167-a-K97N mutant, unlike the wild type, localizes in the cytoplasm and does not promote perinuclear lysosomal clustering. Furthermore, cells expressing RNF167-a-K97N exhibit dispersed lysosomes, increased exocytosis and enhanced plasma membrane repair. Interestingly, these functional features of RNF167-a-K97N were shared with a naturally occurring short version of RNF167 (isoform RNF167-b). In brief, the results presented here reveal a novel role of RNF167-a, as well as its natural variants RNF167-a-K97N and RNF167-b, as an upstream regulator of lysosomal exocytosis and plasma membrane resealing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/jcs.239335DOI Listing
June 2020

The ubiquitin ligase FBXW7 targets the centriolar assembly protein HsSAS-6 for degradation and thereby regulates centriole duplication.

J Biol Chem 2020 04 21;295(14):4428-4437. Epub 2020 Feb 21.

School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Vithura, Thiruvananthapuram 695551, Kerala, India

Formation of a single new centriole from a pre-existing centriole is strictly controlled to maintain correct centrosome number and spindle polarity in cells. However, the mechanisms that govern this process are incompletely understood. Here, using several human cell lines, immunofluorescence and structured illumination microscopy methods, and ubiquitination assays, we show that the E3 ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7), a subunit of the SCF ubiquitin ligase, down-regulates spindle assembly 6 homolog (HsSAS-6), a key protein required for procentriole cartwheel assembly, and thereby regulates centriole duplication. We found that FBXW7 abrogation stabilizes HsSAS-6 and increases its recruitment to the mother centriole at multiple sites, leading to supernumerary centrioles. Ultrastructural analyses revealed that FBXW7 is broadly localized on the mother centriole and that its presence is reduced at the site where the HsSAS-6-containing procentriole is formed. This observation suggested that FBXW7 restricts procentriole assembly to a specific site to generate a single new centriole. In contrast, during HsSAS-6 overexpression, FBXW7 strongly associated with HsSAS-6 at the centriole. We also found that SCF interacts with HsSAS-6 and targets it for ubiquitin-mediated degradation. Further, we identified putative phosphodegron sites in HsSAS-6, whose substitutions rendered it insensitive to FBXW7-mediated degradation and control of centriole number. In summary, SCF targets HsSAS-6 for degradation and thereby controls centriole biogenesis by restraining HsSAS-6 recruitment to the mother centriole, a molecular mechanism that controls supernumerary centrioles/centrosomes and the maintenance of bipolar spindles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.AC119.012178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135989PMC
April 2020

Corrigendum to "Sodium alginate/poly(vinyl alcohol)/nano ZnO composite nanofibers for antibacterial wound dressings" [Int. J. Biol. Macromol., 49 (2011) 247-254].

Int J Biol Macromol 2019 08 7;134:1218. Epub 2019 May 7.

Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Ponekkara, Kochi 682041, India. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2019.04.152DOI Listing
August 2019

Antibacterial and bioactive alpha- and beta-chitin hydrogel/nanobioactive glass ceramic/nano silver composite scaffolds for periodontal regeneration.

J Biomed Nanotechnol 2013 Nov;9(11):1803-16

Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.

Alveolar bone loss and bone defects are the commonly encountered periodontal problems. Large defects do not heal spontaneously and thus require surgical interventions with bone substitutes. Bone grafts have the disadvantages of eliciting an immunologic response with subsequent graft rejection. The success rate of Guided Tissue Regeneration (GTR) is variable because of high susceptibility to infection. Thus emerged the important role of synthetic biomaterials and hence for this purpose we developed a nanocomposite scaffold, using alpha- and beta-chitin hydrogel with bioactive glass ceramic nanoparticles (nBGC) and silver nanoparticles (nAg) by lyophilization technique (aalpha and beta-chitin hydrogel/nBGC/nAg nanocomposite scaffold). The prepared nanoparticles and nanocomposite scaffolds were characterized. In addition, the porosity, swelling, mechanical properties, antibacterial activity, in vitro degradation and biomineralization, cell viability, cell attachment and cell proliferation ability of the prepared composite scaffolds were also evaluated. The results showed that alpha- and beta-chitin/nBGC/nAg composite scaffolds were porous and have the capacity to absorb fluids and swell. The composite scaffolds also showed enhanced antibacterial activity, bioactivity and controlled degradation in comparison to the control scaffolds. Cell viability studies proved the non-toxic nature of the nanocomposite scaffolds. Cell attachment and cell proliferation studies revealed the attachment and spreading nature of cells. All these studies revealed that, these antibacterial nanocomposite scaffolds could be a promising approach for the management of periodontal defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jbn.2013.1658DOI Listing
November 2013

Sodium alginate/poly(vinyl alcohol)/nano ZnO composite nanofibers for antibacterial wound dressings.

Int J Biol Macromol 2011 Oct 27;49(3):247-54. Epub 2011 May 27.

Amrita Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682 041, India.

Sodium alginate (SA)/poly (vinyl alcohol) (PVA) fibrous mats were prepared by electrospinning technique. ZnO nanoparticles of size ∼160nm was synthesized and characterized by UV spectroscopy, dynamic light scattering (DLS), XRD and infrared spectroscopy (IR). SA/PVA electrospinning was further carried out with ZnO with different concentrations (0.5, 1, 2 and 5%) to get SA/PVA/ZnO composite nanofibers. The prepared composite nanofibers were characterized using FT-IR, XRD, TGA and SEM studies. Cytotoxicity studies performed to examine the cytocompatibility of bare and composite SA/PVA fibers indicate that those with 0.5 and 1% ZnO concentrations are less toxic where as those with higher concentrations of ZnO is toxic in nature. Cell adhesion potential of this mats were further proved by studying with L929 cells for different time intervals. Antibacterial activity of SA/PVA/ZnO mats were examined with two different bacteria strains; Staphylococcus aureus and Escherichia coli, and found that SA/PVA/ZnO mats shows antibacterial activity due to the presence of ZnO. Our results suggest that this could be an ideal biomaterial for wound dressing applications once the optimal concentration of ZnO which will give least toxicity while providing maximum antibacterial activity is identified.f.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2011.04.005DOI Listing
October 2011
-->