Cell Junctions

• Tight Junctions :

  • contain strands of cloudin and occludin

  • example = blood-brain-barrier

• Adherens :

  • strong mechanical

  • peristalsis

  • uses classical cadherins to link cytoskeleton ➡️ actin

• Desmosomes :

  • stronger than adherens

  • tissue rigidity

  • uses non-classical cadherins to link cytoskeleton ➡️ intermediate filaments

  • cardiac muscle , skin

• Hemidesmosomes :

  • uses integrins to link cytoskeleton ➡️ basal lamina intermediate filaments

• Gap Junctions :

  • facillitate communication

  • synchronized heart beat

  • allow electricity , ATP , misc things to pass

  • 6 trans membrane domains

  • connected by connexins

GPCR

• $G_i$$G_i$ = inhibitory

  1. Signal Molecule binds and Activates GPCR ( $G_i$$G_i$ )

  2. binds and inhibits adenylyl cyclase

  3. reduces PKA activation

  4. reduces cell response ( gene transcription )

• $G_s$$G_s$ = stimulatory

  1. Signal Molecule binds and Activates GPCR ( $G_s$$G_s$ )

  2. binds and stimulates adenylyl cyclase

  3. increases PKA activation

  4. increases cell response ( gene transcription )

• $G_q$$G_q$ = activates PLC via DAG and IP3

  1. Signal Molecule binds and Activates GPCR ( $G_q$$G_q$ )

  2. $PLC\beta$$PLC \beta$ becomes activated

  3. $\mathrm{PIP}{\phantom{A}}_2\underset{\mathrm{PLC}\beta }{\overset{}{\to }}DAG+I{P}_3$$\ce{PIP_2 ->[][PLC \beta]} DAG + IP_3$

     • this depletes levels of PIP2 in the membrane

     • but voltage gated M-channels ( potassium channels ) need PIP2 in order to open

       • so M-channels close

       • this is a SIGNALING event !

       • the removal of PIP2 closed potassium channels , depolarizes the membrane ,

         • makes it very easy to fire action potential now

         • only a little bit of sodium is need to reach the action potential threshold

  4. DAG then activates PKC

  5. IP3 causes calcium to be released from endoplasmic reticulum

     • the calcium can also reinforce / enhance signaling of PKC

  • 3 Different Ways $G_q$$G_q$ can signal :

    1. Depletion of $PI{P}_2$$PIP_2$ in the membrane

    2. Liberation of $I{P}_3$$IP_3$ and hence intracellular calcium release

    3. Libration of DAG and hence activation of PKC

• Describe one alternative pathway that G-protein activation may signal via

  • Conventional Way = producing signaling molecules

  • Alternative Way = reduction ! of $PI{P}_2$$PIP_2$

Misc

• Cadherins = used in adherins and desmosomes

  • calcium dependent

• Catenins = link cadherins ➡️ actin skeleton

• Integrins = link cytoskeleton ( actin ) ➡️ ECM

Extracellular Matrix Compounds

1. Proteoglycans

2. Fibrinectin

3. Integrins

4. Glycoproteins