General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
This presentation is about the functioning of G-Protein coupled receptors. It also gives necessary information about the G-protein and it functions. It ends by explaining some of the faults associated with GPCR (G-PROTEIN COUPLED RECEPTORS).
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
1.WHAT ARE GPCRs
2. CLASSIFICATION OF GPCRs
3. GPCRs SECOND MESSENGERS
4. GPCRs FAMILIES
5. STRUCTURE IF GPCRs
6. DRUG TARGETS OF GPCRs
7. CONCLUSION
8. REFERENCES
9. THANKS
General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
This presentation is about the functioning of G-Protein coupled receptors. It also gives necessary information about the G-protein and it functions. It ends by explaining some of the faults associated with GPCR (G-PROTEIN COUPLED RECEPTORS).
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
1.WHAT ARE GPCRs
2. CLASSIFICATION OF GPCRs
3. GPCRs SECOND MESSENGERS
4. GPCRs FAMILIES
5. STRUCTURE IF GPCRs
6. DRUG TARGETS OF GPCRs
7. CONCLUSION
8. REFERENCES
9. THANKS
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
Lecture 7 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University.
This presentation contains a detail account on how any drug acts and what are the receptors, its type etc. this may be helpful for quick understanding (digramatic).
Lecture 6 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Includes neurotransmitter release, reuptake, and inactivation
This is for review of posture and gait cycle and at the end something about crossed syndromes and quick guide for treatment as stretching and strengthening exercises to fix issues
This presentation is about signal processing in the nervous system, pain control, ascending and descending pathways in spinal cord, cerebrum cerebellum, limbic system,....
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
32. Osmotic pressure
• Based on decrease in freezing point
• A one molar solute -1.86⁰ C
• Plasma… -0.52
• 280mmol
• pv=nRT, p×1=1×62.63×310
• A one molar solute 19200mmHg
• Osmotic pressure of plasma?
• 5600mmHg
33. Could a hyperosmolar solution be isotonic?
• Yes
• Because tonicity depend on permeability of
the membrane
35. Simple & facilitated diffusion
Simple diffusion Facilitated diffusion
No saturation Saturation(Vmax)
Fast Low velocity
Chemical gradient Carrier protein
Linear correlation Non-linear correlation
Competition
61. Potassium channels in AP
• Delayed rectifier K ch
– In repolarization
• Early K ch
– Reduce the velocity of depolarization
• Calcium-activated K ch
– Preventing repetitive stimulation
87. Functions of the electrical transmission
1.Electrical synapses are more reliable, less likely to fail.
2.Greater speed –important in rapid reflexes involving escape reactions.
3.The synchronization of electrical activity of groups of cells.
4.Intracellular transfer of molecules such as Ca, ATP and cAMP.
5.The activity of gap junctions between cells in the retina can be modulated by
dopamine. Thus the gap junctions can be dynamic components of neuronal
circuits.
6. Mutations in the genes encoding gap junction proteins cause diseases:
•Peripheral neuropathy –Charcot-Marie-Tooth disease
•Abnormal cardiac development
•Congenital deafness
Charcot-Marie-Tooth disease –inherited peripheral neuropathy
-degeneration of peripheral nerves
-Foot deformities, muscle wasting, distal sensory loss, decreased tendon
reflexes
Gap junction is necessary for radial migration in the neocortex
90. Chemical synapse
• neurotransmitter
• Depolarization of the presynaptic nerve
terminal
• Triggers the release of molecules Interact with
receptors on the postsynaptic neuron
• Excitation or inhibition of the postsynaptic
neuron.
91. Neurotransmitters:
Definition:
• Synthesized by presynaptic neuron
• Released by stimulation
• Microapplication of NT. Mimic the presyn. stimulation
• Presynaptic & microappl. Stim. Must be blocked by
pharmacologic agent
• High affinity uptake mechanism for the substance in
synaptic terminal
release of NT, synapsin
6/9/2010 91
93. Receptors of NTs
• Ionotropic: • Metabotropic:
ligand gating i.e. nicotinic work by second
receptor (inhibited by messenger
curare) (G protein)
6/9/2010 93
104. Excitotoxicity
• High demand of brain cells to oxygen & glucose
• Cardiac arrest, stroke, …..
• Limits of ATP
• Depolarizing the membrane
• Calcium leak into cells
• Glutamate release
• Depolarization
• More calcium
• ……………
• Cell death
131. Cell-to-cell communication by extracellular
signaling usually involves six steps
• Synthesis of the signaling molecule by the signaling cell
• Release of the signaling molecule by the signaling cell
• Transport of the signal to the target cell
• Detection of the signal by a specific receptor protein
• A change in cellular metabolism, function, or development
triggered by the receptor-signal complex
• Removal of the signal, which usually terminates the cellular
response
135. Signal transduction steps
• Ligand binds to the receptor
• Dissociation of a subunit from b & g
• Exchanging GDP with GTP
• Moving a subunit
• Activation of adenylyl cyclase or GC
• Second messenger( cAMP)
• Binding cAMPs to R subunit of Protein kinase
• Dissociation & activation of C subunit
• Phosphorylation of target protein
• Cell response
142. hormone
signal
outside
GPCR plasma
The a subunit of membrane
a G-protein (Ga) a g g a cytosol
binds GTP, & can AC
GDP b b GTP
hydrolyze it to
GDP + Pi. GTP GDP ATP cAMP + PPi
a & g subunits have covalently attached lipid anchors that
bind a G-protein to the plasma membrane cytosolic surface.
Adenylate Cyclase (AC) is a transmembrane protein, with
cytosolic domains forming the catalytic site.
143. hormone
signal
outside
GPCR plasma
membrane
a g g a cytosol
AC
GDP b b GTP
GTP GDP ATP cAMP + PPi
The sequence of events by which a hormone activates
cAMP signaling:
1. Initially Ga has bound GDP, and a, b, & g subunits
are complexed together.
Gb,g, the complex of b & g subunits, inhibits Ga.
144. hormone
signal
outside
GPCR plasma
membrane
a g g a cytosol
AC
GDP b b GTP
GTP GDP ATP cAMP + PPi
2. Hormone binding, usually to an extracellular domain
of a 7-helix receptor (GPCR), causes a conformational
change in the receptor that is transmitted to a G-protein
on the cytosolic side of the membrane.
The nucleotide-binding site on Ga becomes more accessible
to the cytosol, where [GTP] > [GDP].
Ga releases GDP & binds GTP (GDP-GTP exchange).
145. hormone
signal
outside
GPCR plasma
membrane
a g g a cytosol
AC
GDP b b GTP
GTP GDP ATP cAMP + PPi
3. Substitution of GTP for GDP causes another
conformational change in Ga.
Ga-GTP dissociates from the inhibitory bg complex & can
now bind to and activate Adenylate Cyclase.
147. KD values for cell-surface hormone receptors
approximate the concentration of circulating hormones
148.
149. G protein-coupled receptors and their
effectors
• Many different mammalian cell-surface receptors are
coupled to a trimeric signal-transducing G protein
• Ligand binding activates the receptor, which activates the G
protein, which activates an effector enzyme to generate an
intracellular second messenger
• All G protein-coupled receptors (GPCRs) contain 7
membrane-spanning regions with their N-terminus on the
exoplasmic face and C-terminus on the cytosolic face
• GPCRs are involved in a range of signaling pathways,
including light detection, odorant detection, and detection of
certain hormones and neurotransmitters
154. Adenylyl cyclase is stimulated and inhibited by
different receptor- ligand complexes
155. Types of G-proteins
• Ras (growth factor signal cascades)
• Rab (membrane vesicle targeting and fusion)
• ARF (formation of vesicle coatomer coats)
• Ran (transport of proteins into & out of the nucleus)
• Rho (regulation of actin cytoskeleton)
158. Receptor tyrosine kinases and Ras
• Receptor tyrosine kinases recognize soluble or membrane
bound peptide/protein hormones that act as growth factors
• Binding of the ligand stimulates the receptor’s tyrosine
kinase activity, which subsequently stimulates a signal-
transduction cascade leading to changes in cell physiology
and/or patterns of gene expression
• RTK pathways are involved in regulation of cell proliferation
and differentiation, promotion of cell survival, and modulation
of cellular metabolism
• RTKs transmit a hormone signal to Ras, a GTPase switch
protein that passes on the signal on to downstream
components