Cell Signaling; Communication at the Molecular level

After this lecture, student will be able to understand why a signaling system is required for living organisms

At the end of this lecture, students will be able to understand the importance of a signaling system for living organisms

In this lecture, the students will learn about the different types of signaling; Paracrine, autocrine, endocrine and neuronal signaling

Ligands (signaling molecules) are the molecules, released by signaling cells, that are responsible for transmitting information between cells and within a cell in the body. Ligands interact with proteins in target cells, are also called as receptors. Ligands and receptors exist in several varieties; however, a specific ligand will have a specific receptor that typically binds only that ligand. This lecture, part 1, will introduce you to the basics of ligands and receptors

This is the continuation of the previous lecture and will further dive into the explanation of ligands and receptors

This lecture is an example of signaling from the unicellular world, to appreciate that signaling is also important in the unicellular world. This lecture will use "mating of haploid yeast cells" as an example for understanding this concept 

Protein kinases (PTKs) are enzymes that regulate the biological activity of proteins by phosphorylation of specific amino acids with ATP as the source of phosphate, thereby inducing a conformational change from an inactive to an active form of the protein or vice versa. At the end of this lecture, students will be able to classify kinases into different types

Fibroblast Growth Factors (FGFs), are a family of cell signaling proteins with members involved in angiogenesis (It is the physiological process through which new blood vessels form from pre-existing vessels), wound healing, embryonic development, acts as a mitogen and in various endocrine signaling pathways. This lecture will focus on the structure and function of FGF along with its receptor, FGFR

Non-receptor tyrosine kinases (nRTKs) are cytosolic enzymes that are responsible for catalyzing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in target proteins. This lecture will use SRC protein as an example to help students understand the function of nRTKs.

This is the first lecture on the series on the cell cycle. The cell cycle is a 4-stage process consisting of Gap 1 (G1), Synthesis, Gap 2 (G2) and mitosis. An active eukaryotic cell will undergo these steps as it grows and divides. After completing the cycle, the cell either starts the process again from G1 or exits the cycle through G0.

At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK) and switch between active and inactive states depending on the need of the body. They are Activated by several mechanisms including Activator binding, Phosphorylation of active sites and Dephosphorylation of inhibitory phosphatases. This lecture will explain Receptor serine / threonine kinases and TGF β 1 pathway to help student understand its function

This is continuation of the previous lecture and will conclude the topic of transforming growth factor beta and its pathway

Karyopherins are a group of proteins involved in transporting molecules between the cytoplasm and the nucleus of a eukaryotic cell. The inside of the nucleus is called the karyoplasm (nucleoplasm). Generally, karyopherin mediated transport occurs through the nuclear pore, which acts as a gateway into and out of the nucleus. Most proteins require karyopherins to traverse the nuclear pore. Karyopherins can act as Importins (helping proteins get into the nucleus) or Exportins (helping proteins get out of the nucleus). They belong to Nuclear Pore Complex Family in the Transporter Classification Database (TCDB). The energy for transport is derived from the Ran gradient. 

Importin is a type of protein that moves other protein molecules into the nucleus by binding to a specific recognition sequence, called the Nuclear Localization Signal (NLS) [This signal consists of one or more short sequences of positively charged lysine or arginine exposed on the protein surface].

The exportins are a class of karyopherins which binds to a 'cargo' protein in the nucleus of a cell and transports it through the nuclear pore complex to the cytoplasm. The protein that has to exported to the cytoplasm have a specific recognition sequence known as Nuclear Export Signal (NES). The NES is a short amino acid sequence of 4 hydrophobic [glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, and tryptophan] residues in a protein that targets it for export from the cell nucleus to cytoplasm through the nuclear pore complex using nuclear transport. It has the opposite effect of a Nuclear Localization Signal, which targets a protein located in the cytoplasm for import to the nucleus

Protein kinase A (PKA), also known as cAMP dependent Protein kinase, is a Serine/Threonine kinase and primary target of cAMP and is involved in the regulation of sugar and lipid metabolism, ion channel activities and nerve synaptic transduction. This topic has been covered in five videos including this one.

This is the 2nd video in the series of Protein Kinase A and is focusing on Myristoylation and geranylgeranylation

This is the third video on PKA and is focusing on Activation of Receptor and Adenylyl Cyclase.

This is the 4th video on PKA and is focusing on the Structure of PKA and its activation by cAMP.

This is the 5th video on PKA and is focusing on Phosphorylase Kinase and Glycogen Phosphorylase activation by PKA.

This is the 1st video in the series of videos on Protein Kinase C (PKC) and is focusing on the Introduction, Production of DAG and IP3, and Calcium homeostasis. Increases in intracellular Ca2+ concentrations are often a result of IP3 activation. When a ligand binds to a G protein-coupled receptor (GPCR) that is coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme Phosphoinositide phospholipase C [PLC-β], which results in the cleavage of PIP2 [Phosphatidyl inositol 4, 5 bisphosphate] into IP3 [inositol 1,4,5-trisphosphate] and Di Acyl Glycerol [DAG]. IP3 is a soluble molecule and is capable of diffusing through the cytoplasm to the ER, or the Sarcoplasmic reticulum (SR) in the case of muscle cells, once produced by PLC. Once at the ER, IP3 is able to bind to Inositol Triphosphate Receptor [Ins3PR]on a ligand-gated Ca2+ channel that is found on the surface of the ER. The binding of IP3 to InsP3R triggers the opening of the Ca2+ channel and the release of Ca2+ into the cytoplasm and a cascade of the pathway can be generated

This is the 2nd video on Protein Kinase C (PKC) and is focusing on the Protein Kinase C, Ca2+ /Calmodulin complex and CaM Kinase-II

Structure of a Neuron The neuron is the basic building block of the brain and central nervous system. Neurons are specialized cells that transmit chemical and electrical signals. The brain is made up entirely of neurons and glial cells, which are non-neuronal cells that provide structure and support for the neurons. Nearly 86 billion neurons work together within the nervous system to communicate with the rest of the body. They are responsible for everything from consciousness and thought to pain and hunger. Neurons are similar to other cells in the body because: Neurons are surrounded by a cell membrane. Neurons have a nucleus that contains genes. Neurons contain cytoplasm, mitochondria and other organelles. Neurons carry out basic cellular processes such as protein synthesis and energy production.

There are three primary types of neuron a. Sensory neurons: responsible for converting external stimuli (like heat, sound) from the environment into corresponding internal stimuli. b. Motor neurons: located in the Central Nervous System (CNS); they project their axons outside of the CNS to directly or indirectly control muscles. c. Interneurons: act as the “middle men” between sensory and motor neurons

I hope the explanation in this video does not get too complicated, but it is important to understand how neurons do what they do. There are many details, but go slow and look at the figures. Much of what we know about how neurons work comes from experiments on the giant axon of the squid. This giant axon extends from the head to the tail of the squid and is used to move the squid's tail. How giant is this axon? It can be up to 1.5mm in diameter; easy to see with naked eye. Action Potential (Resting Membrane Potential, Depolarization, Repolarization, hyperpolarization, Threshold) and Sodium Potassium Pump. Neurons send messages electrochemically. This means that chemicals cause an electrical signal. Chemicals in the body are "electrically-charged" when they have an electrical charge, they are called ions. The important ions in the nervous system are sodium and potassium (both have 1 positive charge, +), calcium (has 2 positive charges, ++) and chloride (has a negative charge, -). There are also some negatively charged protein molecules. It is also important to remember that nerve cells are surrounded by a membrane that allows some ions to pass through and blocks the passage of other ions. This type of membrane is called semi-permeable.

This is the 4th part on the neuronal signaling and is focusing on the release of Neurotransmitter at the synaptic cleft. At rest, neurotransmitter-containing vesicles are stored at the terminal of the neuron in one of two places. A small number of vesicles are positioned along the pre-synaptic membrane in places called "active zones." This is where neurotransmitter release occurs. Most vesicles, however, are held close to these zones, yet further from the membrane itself until they are needed. These vesicles are held in place by Ca2+ sensitive vesicle membrane proteins (VAMPs), which bind to actin filaments, microtubules, and various other elements of the cytoskeleton. When an action potential reaches the terminal of a presynaptic neuron, voltage-dependent calcium (Ca2+) channels embedded in the pre-synaptic membrane open and Ca2+ rushes in. This influx of calcium ions triggers a series of events, which ultimately results in the release of the neurotransmitter from a storage vesicle into the synaptic cleft.

This video is about the machinery of the cell cycle. Cell cycle is a highly regulated process. Timing progression of cell cycle through different phases, G0, G1 S, G2, and M requires an orchestrated functions of several elements, including cyclins, cyclin-dependent kinases (CDKs), retinoblastoma protein (Rb; pocket proteins) and E2F complex proteins

This is the 3rd lecture in the series of lectures on cell cycle and will describe an introduction to the cell cycle control system

This video is about the events happening in G1 phase of the cell cycle. During G1 phase, the cell grows in size and synthesizes mRNA and proteins (known as histones) that are required for DNA synthesis. Once the required proteins and growth are complete, the cell enters the next phase of the cell cycle, S phase.

This video is going to tell you how p53 halts the cell cycle in the G1 phase when DNA is damaged. p53 is activated by DNA damage and causes production of a Cdk inhibitor, which binds to the Cdk-G1/S cyclin complex and inactivates it. This halts the cell in G1 and prevents it from entering S phase, allowing time for the DNA damage to be fixed.

This video will you about the function of G1-S CDK and S-CDK. During the G1 phase, Cyclin-dependent kinase (CDK) activity promotes DNA replication and initiates the G1-to-S phase transition. ... G1–S transcripts encode proteins that regulate downstream cell cycle events.

This video is about the events in the S and G2 phases of the cell cycle. S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between the G1 phase and the G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved.

This video will tell you how G2 phase is working as a preparatory phase for the M phase of the cell cycle. Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S. pombe, where it is encoded by genes cdc28 and cdc2, respectively. In humans, Cdk1 is encoded by the CDC2 gene. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates (over 75 have been identified in budding yeast); phosphorylation of these proteins leads to cell cycle progression

This video is about the functions of M-CDK (CDK1+ Cyclin B) at the start of M-Phase

This video is about the events in the metaphase of the cell cycle. In metaphase, chromosomes line up at the metaphase plate, under tension from the mitotic spindle. The two sister chromatids of each chromosome are captured by microtubules from opposite spindle poles. In metaphase, the spindle has captured all the chromosomes and lined them up at the middle of the cell, ready to divide.

This video is about the role of spindle assembly checkpoint. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation

This video is about the functions of Anaphase promoting complex and contractile ring

The ubiquitin-proteasome pathway (UPP) is one of the major destruction ways to control the activities of different proteins. The function of UPP is to eliminate dysfunctional/misfolded proteins via the proteasome, and these specific functions enable the UPS to regulate protein quality in cells.