Nagaraj Balasubramanian- MSc, PhD
- Professor at Indian Institute of Science Education and Research Pune
Nagaraj Balasubramanian
- MSc, PhD
- Professor at Indian Institute of Science Education and Research Pune
www.adhesionlab.com
About
44
Publications
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Introduction
As a cell biologist by training, I completed my PhD in Biochemistry from the Cancer Research Institute at the Tata Memorial Center. After a postdoc in mammalian phototransduction (University of Miami) and cell adhesion and trafficking (University of Virginia), I moved to IISER, Pune, to work on cell adhesion-mediated regulation of trafficking and organelle function and its implications for cell migration and anchorage dependence. We are also interested in how it is deregulated in cancers.
Current institution
Additional affiliations
Position
- Professor (Associate)
Description
- Associate Professor of Biology
September 2017 - October 2019
Publications
Publications (44)
Cell-matrix adhesion regulates Golgi organization through Arf1-mediated dynein recruitment, maintaining its juxtanuclear localization. On loss of adhesion, Arf1 activation drops, causing loss of dynein, promoting differential disorganization of cis- vs trans-Golgi along microtubules. Golgi regulates microtubule nucleation and stability. In fibrobla...
Arf‐like GTPases (Arls) regulate membrane trafficking and cytoskeletal organization. Genetic studies predicted a role for Arl15 in type‐2 diabetes, insulin resistance, adiposity, and rheumatoid arthritis. Cell biological studies implicated Arl15 in regulating various cellular processes, including magnesium homeostasis and TGFβ signaling. However, t...
Cell-matrix adhesion regulates membrane trafficking, Golgi organisation and function. Differential Golgi organisation in cancer cells could drive changes in trafficking and processing of cargoes. A simple screen evaluating Golgi organisation identifies breast (MDAMB231 vs MCF7) and lung cancer (A549 vs CaLu1) cell line pairs with differently organi...
The sulfane sulfur pool, comprised of persulfide (RS‐SH) and polysulfide (RS‐SnH) derived from hydrogen sulfide (H2S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve as significant cellular redox hubs, mediate stress response and cellular health. However, the effects of endogenous mitochondrial s...
The sulfane sulfur pool, comprised of persulfide (RS‐SH) and polysulfide (RS‐SnH) derived from hydrogen sulfide (H2S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve as significant cellular redox hubs, mediate stress response and cellular health. However, the effects of endogenous mitochondrial s...
Complex sugar polymers known as glycans contribute to the high molecular diversity of the eukaryotic cell surface. The types and levels of glycans on one cell can be sensed by other cells using carbohydrate-specific binding proteins such as lectins, enabling glycans to regulate cell-cell interactions. Glycans are covalently assembled onto proteins...
Fibroblasts embedded in a 3D matrix microenvironment can remodel the matrix to regulate cell adhesion and function. Collagen hydrogels are a useful in vitro system to study cell–matrix interactions in a 3D microenvironment. While major matrix reorganizations are easily recognizable, subtle changes in response to environmental or biochemical cues ar...
Arf1 belongs to the Arf family of small GTPases that localise at the Golgi and plasma membrane. Active Arf1 plays a crucial role in regulating Golgi organisation and function. In mouse fibroblasts, loss of adhesion triggers a consistent drop (∼50%) in Arf1 activation that causes the Golgi to disorganise but not fragment. In suspended cells, the tra...
The extracellular matrix in the tumour microenvironment can regulate cancer cell growth and progression. A pan-cancer analysis of TCGA data from 30 cancer types, identified the top 5% of matrisome genes with amplifications or deletions in their copy number, that affect their expression and cancer survival. A similar analysis of matrisome genes in i...
Arf-like GTPases (Arls) regulate membrane trafficking and cytoskeletal organization. Genetic studies predicted a role for Arl15 in type-2 diabetes, insulin resistance, adiposity, and rheumatoid arthritis. Recent studies indicate a possible role for Arl15 in multiple physiological processes, including magnesium homeostasis. However, the molecular fu...
The extracellular matrix (ECM) is a complex network of macromolecular proteins and proteoglycans that have a vital structural and functional role in cell and tissue organization. Cells attached to or embedded in the ECM respond to biochemical and mechanical cues from the ECM to regulate cellular function, including migration. Cells respond not just...
Purpose:
Previous studies assessing fibroblast interactions with implants have mainly relied on measurements such as cell migration, gene expression, and cell adhesion. For these studies, testing cellular behavior at the implant surface was done by imaging the cell-implant interface using standard microscopy techniques in 2D tissue culture dishes....
Aurora kinases despite their similarity have distinct roles in the cell cycle, which is regulated by cell-matrix adhesion and growth factors. This study reveals loss of adhesion and re-adhesion to differentially regulate Aurora kinases. AURKB activation that drops on the loss of adhesion recovers on re-adhesion in serum-deprived conditions but not...
Aurora kinases despite their similarity have distinct roles in the cell cycle, which is regulated by cell-matrix adhesion and growth factors. This study reveals loss of adhesion and re-adhesion to differentially regulate Aurora kinases. AURKB activation that drops on the loss of adhesion recovers on re-adhesion in serum-deprived conditions but not...
The extracellular matrix as part of the tumor microenvironment can regulate cancer cell growth and progression. Using TCGA data from 30 cancer types, the top 5% of matrisome genes with amplifications or deletions that affect survival in cancers were identified. Eight of these genes show altered expression in ~50% or more cancers affecting survival...
Integrin‐mediated adhesion regulates cellular responses to changes in the mechanical and biochemical properties of the extracellular matrix. Cell–matrix adhesion regulates caveolar endocytosis, dependent on caveolin 1 (Cav1) Tyr14‐phosphorylation (pY14Cav1), to control anchorage‐dependent signaling. We find that cell–matrix adhesion regulates pY14C...
The plasma membrane is a dynamic lipid bilayer that engages with the extracellular microenvironment and intracellular cytoskeleton. Caveolae are distinct plasma membrane invaginations lined by integral membrane proteins Caveolin1, 2, and 3. Caveolae formation and stability is further supported by additional proteins including Cavin1, EHD2, Pacsin2...
Epidermal Growth Factor Receptor (EGFR) is a known promoter of tumor progression and is overexpressed in lung cancers. Growth factor receptors (including EGFR) are known to interact with extracellular matrix (ECM) proteins, which regulate their activation and function. Fibulin-1 (FBLN1) is a major component of the ECM in lung tissue, and its levels...
More than 2,000 dental implant options are estimated to be available for any given clinical situation. Because many implants have claims that are substantiated mainly on the basis of in vitro studies, it is prudent for clinicians to understand the interpretation of such studies and possible clinical relevance. In vitro tests can be segregated as su...
Cell-matrix adhesion regulates membrane trafficking controlling anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its regulation by adhesion remains unclear. Here we report that loss of adhesion dramatically disorganized the Golgi in mouse and human fibroblast cells. Golgi integrity is restored rapidly upo...
The small GTPase RalA is a known mediator of anchorage-independent growth in cancers and differentially regulated by adhesion and Aurora Kinase A (AURKA). Inhibiting AURKA hence offers a means of specifically targeting RalA (over RalB) in cancer cells. MLN8237 (alisertib) is a known inhibitor of Aurora Kinases, its specificity for AURKA, however, i...
Cell-matrix adhesion regulates membrane trafficking to control anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its control by adhesion remains untested. We find the loss of adhesion rapidly disorganizes the Golgi in mouse and human fibroblast cells, its integrity restored rapidly on re-adhesion to fibron...
Integrins play a vital role in regulating cell adhesion that drives cell attachment, spreading, and migration. They do so by recruiting and activating several downstream signaling pathways that control actin cytoskeleton remodelling, endocytic and exocytic trafficking, and membrane organization in cells. The spatial and temporal nature of this regu...
Supplementary sequence information.
Supplementary Fig. S1: Representative blot showing knockdown of (A) RalA, (B) RalB and (C) Arf6 relative to tubulin (WB: Tubulin). (D) Representative western blot showing the detection of endogenous RalA in RalA knockdown MEFs (RalAi) expressing HA tagged hRalA* mutant resistant to siRNA (indicated by arrow) (RalAi + hRalA*). Western blot detection...
List of primers used in RT-qPCR analysis.
List of up- and down-regulated genes and Functional Annotation Clustering of up- and down-regulated genes in Ip6k1−/− MEFs when compared with Ip6k1+/+ MEFs.
Integrin dependent regulation of growth factor signalling confers anchorage dependence that is deregulated in cancers. Downstream of integrins and oncogenic Ras the small GTPase Ral is a vital mediator of adhesion dependent trafficking and signalling. This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function...
Inositol hexakisphosphate kinases (IP6Ks), a family of enzymes found in all eukaryotes, are responsible for the synthesis of 5-diphosphoinositol pentakisphosphate (5-IP7) from inositol hexakisphosphate (IP6). Three isoforms of IP6Ks are found in mammals, and gene deletions of each isoform lead to diverse, non-overlapping phenotypes in mice. Previou...
Multi-drug delivery based on polymer nano-scaffolds is an essential protocol to be developed for better administration of anticancer drugs to enhance their therapeutic efficacies against cancer cells. Here, we report dual delivery polysaccharide nano-vesicles that are capable of loading and delivering both water soluble and water insoluble drugs to...
Dextran vesicular nano-scaffolds were developed based on polysaccharide and renewable resource alkyl tail for dual encapsulation of hydrophilic and hydrophobic molecules (or drugs) and delivery into cells. The roles of the hydrophobic segments on the molecular self-organization of dextran backbone into vesicles or nanoparticles were investigated in...
Anchorage dependence of cell growth is a key metastasis-suppression mechanism that is mediated by effects of integrins on growth signaling pathways. The small GTPase RalA is activated in metastatic cancers through multiple mechanisms and specifically induces anchorage independence. Loss of integrin-mediated adhesion triggers caveolin-dependent inte...
Integrin-mediated adhesion regulates membrane binding sites for Rac1 within lipid rafts. Detachment of cells from the substratum triggers the clearance of rafts from the plasma membrane through caveolin-dependent internalization. The small GTPase Arf6 and microtubules also regulate Rac-dependent cell spreading and migration, but the mechanisms are...
The properties of cholesterol-dependent domains (lipid rafts) in cell membranes have been controversial. Because integrin-mediated cell adhesion and caveolin both regulate trafficking of raft components, we investigated the effects of adhesion and caveolin on membrane order. The fluorescent probe Laurdan and two-photon microscopy revealed that foca...
Growth of normal cells is anchorage dependent because signalling through multiple pathways including Erk, phosphatidylinositol-3-OH kinase (PI(3)K) and Rac requires integrin-mediated cell adhesion. Components of these pathways localize to low-density, cholesterol-rich domains in the plasma membrane named 'lipid rafts' or 'cholesterol-enriched membr...
Small GTP binding proteins regulate diverse biological processes including gene expression, cytoskeleton reorganization, and protein and vesicular transport. While small GTPases have been investigated in a wide variety of cells, few studies have addressed their role in photoreceptors. In vertebrate retinal rods, the light stimulus is transmitted fr...
Many lines of evidence show that membranes contain microdomains, "lipid rafts", that are different from the rest of the membrane in specific lipid and protein composition. In several biological systems, they were shown to be necessary for trafficking and signal transduction. Here, we investigate if lipid rafts have a role in the regulation of the G...
Protein kinase C (PKC) is reported to play a role in maturation of the myeloid cell and functions of the mature neutrophil. The neutrophils in chronic myeloid leukemia (CML) exhibit defects in several functions. As a step towards understanding the role of PKC in the defects in function of the leukemic cells, this study investigates the expression o...
In vertebrate photoreceptors, photoexcited rhodopsin interacts with the G protein transducin, causing it to bind GTP and stimulate the enzyme cGMP phosphodiesterase. The rapid termination of the active state of this pathway is dependent upon a photoreceptor-specific regulator of G protein signaling RGS9-1 that serves as a GTPase activating protein...
Neutrophils from patients with Chronic Myeloid Leukemia (CML) exhibit defects in several functions. They also show altered phosphorylation-dephosphorylation patterns of several proteins on stimulation with phorbol myristate acetate--a direct activator of protein kinase C (PKC). Since PKC mediates several functions of the neutrophil, in this study w...
