Cell signalling


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It shares the basics of cell signalling pathways.

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Cell signalling

  1. 1. Preceptors: Dr. Rakesh Sharma Dr. Achint Juneja Presented by: Dr. Tanvi Verma
  2. 2. Content • Definition • Classification • Pathways initiated by lipid soluble messengers • Pathways initiated by water soluble messengers • Signal transduction in Orthodontics • References
  3. 3. Cell Signalling Pathways Various diverse events between cell stimulation and final response are called SIGNALLING PATHWAYS They are also known as Signal transduction pathways
  4. 4. Receptor activation CELLULAR RESPONSE Permeability Metabolism Secretory activity Rate of proliferation and differtiation Contraction
  5. 5. 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
  6. 6. 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 factor Alters the rate of gene transcription mRNA tRNA Protein synthesis
  7. 7. Some common Lipid soluble messengers • Glucocorticoids activates numerous genes involved in cellular metabolism. • Cortisol inhibit genes whose protein products are inflammatory mediators.
  8. 8. 2. Ligand gated ion channels • Receptor protein acts as an ion channel • Seen in; - Nerve-nerve junctions - Neuro-muscular junctions
  9. 9. Ligand binds to ion channel Opening of ion channels Increase diffusion across membrane Change in electrical charge Cell response Contraction/ conduction
  10. 10. 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.
  11. 11. 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
  12. 12. 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
  13. 13. 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
  14. 14. • Effecter proteins could be - adenylyl cyclase - Phospholipase C - Ion channels - cAMP, cGMP - Ca++
  15. 15. 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
  16. 16. Cell Signalling for an Orthodontist
  17. 17. 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)
  18. 18. • 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.
  19. 19. 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.
  20. 20. • 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
  21. 21. 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
  22. 22. Thank you…