Cell signalling
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Transcript of Cell signalling
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Preceptors: Dr. Rakesh SharmaDr. Achint Juneja
Presented by: Dr. Tanvi Verma
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Content
• Definition• Classification• Pathways initiated by lipid soluble messengers• Pathways initiated by water soluble messengers• Signal transduction in Orthodontics
• References
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Cell Signalling Pathways
Various diverse events between cell stimulation and final response are called
SIGNALLING PATHWAYS
They are also known as Signal transduction pathways
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Receptor activation
CELLULAR RESPONSE
Permeability
Metabolism
Secretory activity
Rate of proliferation and
differtiation
Contraction
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Broadly classified as:
Pathways initiated by Hydrophobic messengers
Pathways initiated by Hydrophilic messengers
• Messengers bind to INTRACELLULAR PROTEINS• Eg: Steriod hormone Thyroid hormone Steroid derivatives
• Messengers bind to EXTRACELLULAR PORTIONS of membrane protein• Eg: Most of hormones Neuro-transmitters Paracrine, Autocrine compounds• 4 sub-types:
- Ligand gated ion channels- Intrinsic enzymatic activity- Bounded to janus kinases- G- Protein coupled receptors
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1. Pathways initiated by Lipid soluble messenger
Signal enters the cell
Binds with inactive receptor
Activate the inactivated protein/ receptor
Hormone receptor complex
Binds to specific sequence near a gene
Act as transcription factorAlters the rate of gene transcription
mRNA
tRNA
Protein synthesis
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Some common Lipid soluble messengers
• Glucocorticoidsactivates numerous genes
involved in cellular metabolism.• Cortisol
inhibit genes whose protein products are inflammatory mediators.
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2. Ligand gated ion channels
• Receptor protein acts as an ion channel
• Seen in;- Nerve-nerve junctions- Neuro-muscular junctions
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Ligand binds to ion channel
Opening of ion channels
Increase diffusion across
membrane
Change in electrical
chargeCell responseContraction/
conduction
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3. Receptors with intrinsic enzymatic capacity
• Generally all enzymatic receptors are TYROSINE KINASE with one exception i.e. GUANYLYL CYCLASE
• Guanylyl cyclase catalyses the formation of cGMP (in cytosol) which in turn acts as a second messenger and then leads to phosphorylation.
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4. Cytokines receptors
• There are regulatory proteins• These receptors does not have any
enzymatic activity of their own but their enzymatic action lies in a family of separate cytoplasmic kinases.
• Cascade of phosphorylation leads to cellular response to stimulus
• Mainly involves the Immune system
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5. G-protein coupled receptors
• Largest category• G-protein– heterotrimeric protein– 3 sub-units; alpha, beta, gamma– alpha binds with GDP and GTP– beta and gamma anchor to membrane
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First messenger
Change in conformation of G-
protein
Increase affinity for α to GTP α binds with GTP
Dissociates from other sub-units
Activated α binds to other EFFECTOR
PROTEIN
GTPase of α cleaves GTP to GDP
Inactivation of α subunit
Recombining with beta and gamma
units
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• Effecter proteins could be- adenylyl cyclase- Phospholipase C- Ion channels- cAMP, cGMP- Ca++
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Cell to cell communication is a complex mechanism that has been classified to study
and to understand. A cellular response is generally not because of a single mediator
or messenger but various biochemical processes are involved in transduction
pathways.
These processes are the part of the complex network of communication
that govern basic cellular activities and coordinate the action of cells
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Cell Signalling for
an Orthodontist
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Osteoblast histogenesis and bone formation
Precursor cells
Osteo-progenitor
G1 pre-osteoblast
G2 pre-osteoblast
osteoblast
Overall Osteoblast differentiation takes about 60 hours (Roberts WE, Morey ER; Am J Anat. 174, 1985)
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• G2 pro-osteoblast; D cell is the immediate proliferating progenitor of Osteoblast. (Robert, Mozsary, Klinger: Am J Anat. 165; 1984)• In unstimulated PDL most of the cells are in Go Stage.• This cell reserve gets stimulated under mechanical stimuli.
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Osteoclast recruitment and bone resorption
• There is no evidence to suggests that osteoclasts are produced in PDL.
• Their activity is regulated by:- mechanical stimulus- metabolic stimulus
Robert WE, Chase; 1981 showed that metabolic stimuli produces a rapid response of osteoclast but mechanical stimulation produces a slow but more sustained response.
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• Pro-osteoclasts are derived from marrow by circulating Promonocytes derivatives. (mechanically controlled)
• Osteoclasts are relatively inert cells, they have few biochemical receptor.
• Local mediators are;- PG- Interleukins- Neuro-secretory agents- Growth factors- Calcitonin
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References…
• Orthodontics, current principles and techniques.Graber 5th edition• wiley online library• EJO.oxfordjournals.org• jortho.maneyjournal.org• www.ajodo.org• ncbi.nlm.mih.gov• scholar.google.com• wikipedia
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Thank you…