In response to a variety of extracellular stimuli, actin filament assembly at the leading edge of motile cells causes protrusion during cell crawling and chemotaxis, nerve growth and cell spreading. The actin filament network immediately under the plasma membrane in regions of rapid cellular protrusion consists of short, branched filaments while those deeper in the cortex, as well as at focal adhesions, stress fibers and in microvilli, are much longer and rarely branched (Ref.1). The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and CDC42. The microtubule cytoskeleton is also polarized in a migrating cell, and in addition to organizing the actin[..]

The Tubby protein is the founding member of a multigene protein family that plays an important role in maintenance and function of neuronal cells during development and post-differentiation. Currently, four Tubby gene family members (TUB, TULP1, TULP2 and TULP3) have been identified, which are conserved among different species of mammals (Ref.1). Besides, Tubby-like proteins are also found in other multicellular organisms including plants. These proteins feature a characteristic "Tubby domain" of approximately 260 amino acids at the C-terminus that forms a unique helix-filled barrel structure; this C-terminal domain binds avidly to double-stranded DNA. Most Tubby proteins include NH2-terminal regions that, in general, are not closely related to one another.[..]

Development of a functional cardiovascular system is dependent on the regulated proliferation, migration, and differentiation of endothelial cells in two discrete processes known as vasculogenesis and angiogenesis. Angiogenesis is the formation of new capillaries from pre-existing vessels, whereas vasculogenesis is de-novo capillary formation from EPCs (Endothelial Precursor Cells). New capillaries arise from preexisting larger vessels to give rise to a more complex vascular network with a hierarchy of both large and small vessels (Ref.1). These sequential vascular developments are tightly regulated by a range of pro- and antiangiogenic factors, including VEGF (Vascular Endothelial Growth Factor ), bFGF(basic Fibroblast Growth Factor ), Thrombospondin, Angiopoietins,[..]

Actin Nucleation By ARP-WASP Complex For many cell types, the ability to move across a solid surface is fundamental to their biological function. Certain aspects of cell locomotion, such as the protrusion of the plasma membrane in lamellipodia and filopodia, are driven by the polymerization of actin cytoskeleton. The actin cytoskeleton is a dynamic filament network that is essential for cell movement during embryo development, polarization, morphogenesis, cell division, and immune system function and in the metastasis of cancer cells. To engage in these complex behaviors, cells must direct actin assembly with a high degree of spatial and temporal resolution in response to extracellular signals (Ref.1). To coordinate these behaviors, tight spatial and temporal control[..]

Lymphocytes are one of the five kinds of white blood cells or leukocytes, circulating in the blood. Although mature lymphocytes all look pretty much alike, they are extraordinarily diverse in their functions. The most abundant lymphocytes are: B-Lymphocytes (often simply called B-Cells) and T-Lymphocytes (likewise called T-Cells) [Ref.1]. B-Cells are not only produced in the bone marrow but also mature there. Each B-Cell is specific for a particular antigen. The specificity of binding resides in the BCR (B-Cell receptor) for antigen [Ref.2]. Mature B cells express two BCR isotypes, IgM and IgD. The BCR is composed of mIg (membrane immunoglobulin); a structure of four (in the case of IgD) or five (IgM) immunoglobulin domains in the heavy chain linked by a hinge, and a[..]

The SM (Sphingomyelin) pathway is an evolutionarily conserved stress response system linking diverse environmental stresses (Ultraviolet, Heat Shock, Oxidative Stress, and Ionizing Radiation) to cellular effector pathways. Ceramide is the second messenger in this system and can be generated either by hydrolysis of SM through SM-specific PLC (Phospholipase-C) termed SMases (Sphingomyelinases) or by de novo synthesis through the enzyme Ceramide Synthase . There are two classes of SMase, acidic (A-Smase) and neutral (N-Smase). Stress stimuli such as, TNF-Alpha (Tumor Necrosis Factor-Alpha), lipopolysaccharide, and some chemotherapy drugs such as doxorubicin also mediate apoptosis by generation of the lipid second messenger, Ceramide. A specific interaction between the FAN[..]

The ability of multicellular organisms to maintain cellular homeostasis is critically dependent on a balance between cell survival and cell death (apoptosis). The responsiveness of individual cells to death signals varies greatly depending on the presence of continuous survival cues from the extracellular environment. The perturbation of normal cell survival mechanisms, leading to an increase in cell survival or cell death plays an important role in the development of a number of disease states, including cancer. BAD (BCL2 Associated Death Promoter) is a pro-apoptotic critical regulatory component of the intrinsic cell death machinery that exerts its death-promoting effect upon heterodimerization with the antiapoptotic proteins of the BCL2 family defined by conserved[..]

TGFB (Transforming growth factor-beta) is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-b signals are transmitted through two transmembrane serine/threonine kinase receptors TGFBR1 and TGFBR2 [Ref.1]. Initiation of the TGFB signaling cascade occurs upon ligand binding to TGFB receptor TGFBR2 and subsequent TGFBR1– TGFBR2 heterotetrameric complex formation. TGFBR2 is a constitutively active receptor kinase and phosphorylates Ser/Thr residues in the cytoplasmic GS domain of TGFBR1, which turns on the kinase activity of TGFBR1. Upon Activation, TGFBR1 transmits its signal to the various intracellular SMAD-dependent and SMAD independent signaling[..]

Dynamic regulation of the actin cytoskeleton underpins a multitude of cellular processes, from cell movement and polarization1,2 to cell division.3 The actin cytoskeleton and the proteins involved in its regulation are also fundamentally linked to endocytosis and membrane trafficking.4,5 Members of the Rho family of small GTPases have emerged as important overseers of the actin cytoskeleton and a number of Rho family members and their downstream effector proteins have been linked to specific actin pathways. Among the Rho family actin regulators is Cdc42 is a small GTPase responsible for a large number of eukaryotic cell signaling pathways(Ref.1).CDC42 acts downstream of cell surface receptors to regulate the formation of different F-actin-containing structures. It[..]

Ran is a member of the Ras family of small GTPases. The Ran subgroup is represented by its lone member, Ran, that is distinguished from Ras GTPases by its lipid modification and atypical subcellular localization. Unlike most other Ras-related proteins, Ran is not modified to bind to cell membranes. Instead, Ran protein is localized throughout the cell, where it is concentrated primarily in the nucleus (Ref.1). Ran is regulated by a cytosolic RanGAP1 (Ran GTPase–Activating Protein-1) and by a RanGEF (Chromatin-Bound Guanine Nucleotide Exchange Factor). The distribution of RanGTP provides important spatial information that directs cellular activities during different parts of the cell cycle. During interphase, the localization of RanGEF and RanGAP1 predicts that[..]

Our immune system is largely controlled by the action of pleiotropic cytokines and growth factors, small secreted proteins, which bind to receptors on the surface of immune cells to initiate an appropriate physiological response. The cellular response to cytokines and growth factors is predominantly executed by intracellular proteins known as the Janus kinases (JAKs) and the signal transducers and activators of transcriptions (STATs). These  kinases activated upon ligand binding causes the phosphorylation of tyrosine residues within the receptor intracellular region and phosphorylation of other signalling proteins recruited to the receptor complex like signal transducers and activators of transcriptions (STATs). Once phosphorylated, STATs translocate to the[..]

Calpain is an evolutionary old family of soluble, neutral, calcium-dependent proteases, which have the unique property of using protein cleavage to modify the activity/function of their substrate proteins. There are two major calpain isoforms in the brain, calpain-1 and calpain-2. Calpain-1 and Calpain-2 exhibit opposite functions in both synaptic plasticity and neurodegeneration. Calpain-1 activation is required for the induction of long-term potentiation (LTP) and is generally neuroprotective, while calpain-2 activation limits the extent of potentiation and is neurodegenerative. Calpains release the link between the integrin-dependent FA complex and the actin cytoskeleton by proteolysis of talin, which allows proper cell migration. The activity of Calpains is tightly[..]