Membrane junctions Flashcards
- large, automatic, bidirectional
connexon (functional unit), connexins (protein
subunits)
Allows the movement of 2nd messengers to
trigger a cellular response on the next cell
gap junctions
this is the functional units of gap junctions
connexon
this is the protein subunits of gap junctions
connexins
small, voltage-sensitive
Allows ions (most esp cations), water, and other small molecules to pass through the apical layer of the cell membrane
tight junctions
Links the cytoskeleton of adjacent cells
Functions more as a structural component, than as a membrane junction
Non-discriminatory (allows substances smaller than proteins to pass through)
desmosomes
what are the membrane junctions?
gap junctions, tight junctions, desmosomes
Cells communicate by releasing extracellular
signaling molecules that bind to receptor
proteins located in the plasma membrane,
cytoplasm, or nucleus.
This signal may activate or inactivate
intracellular messengers by interacting with
receptors.
signal transduction
ability to coordinate cellular
activities and function
cell signaling
what are the cellular responses?
Movement
Apoptosis
Synthesis
Differentiation
Metabolism
Secretion
Multiplication
No response (also a response)
TYPES OF INTRACELLULAR SIGNALLING
Electrical
Cell-cell communication
Chemical
direct phone call”
Direct communication via gap junction which
changes a cell’s membrane potential
2 connexons = 12 connexins (6 connexins each) = intercellular channel
E.g. cardiac muscle
electrical signaling
Direct contact between adjacent cells.
Can also compared to a “face to face”
communication
Once the signal is present on the membrane of the cell it will make a physical contact on the
protein found on the target cell.
Important during development and in immune responses.
i.e. Interleukins of T cell
cell-cell communication
what are the goals of cell-cell signaling
- Reaching only the correct recipient(s)
- Imparting the correct information
- Timeliness
- Cause the desired effect
- Effective termination of information
Signals are released in extracellular
compartments (interstitial fluid & vascular
compartment).
Once the signal is in the target cell, it will be
received by a receptor protein.
→ Intracellular receptor
→ Receptors in plasma membrane
Examples: hormones, neurotransmitters, growth factors, and products of cellular metabolism.
chemical signaling
what are the 3 types of chemical signaling?
autocrine
paracrine
endocrine
→ Released signal affects cell of origin or the neighboring cells of the same type.
→ Released to the interstitial fluid
→ i.e. Insulin-like growth factor which is secreted by chondrocytes
autocrine
→ Signal is released by one cell and act on an adjacent cell.
→ The chemical mediators are rapidly metabolized after release thus can only affect cells close to the source.
→ Released to the interstitial fluid like the autocrine.
→ i.e. β cell of the islet of Langerhans
→ Insulin travels to the islet of Langerhans and affect glucagon and somatostatin secretion
paracrine
→ Signal would travel in the bloodstream before it could reach its target cell
→ Similar to radio broadcast
→ i.e. Insulin travels to different organs.
endocrine
what are the cellular receptors?
intracellular receptors and plasma membrane receptors
- For lipid-soluble (hydrophobic) messengers
- Act as transcription factors to alter the rate of transcription of particular genes
For gene transcription and initiation of protein
synthesis
Has longer effects
Inactive receptors are bound by proteins that are dissociated in the presence of its specific ligand
intracellular receptors
- For lipid-insoluble (hydrophilic) messengers
- Purposes/Act as:
→ Ion channels
→ Enzymes
→ Activates Cytoplasmic JAK kinases
→ Activates G protein
→ Act upon effector proteins (either ion
channels or enzymes) in the plasma membrane
plasma membrane receptors
what are the steroid receptors?
cortisol
sex hormones
vitamin D
cytoplasmic/ gated receptor
nuclear receptor
→ Released by adrenal cortex
→ For gluconeogenesis
cortisol
→ Released by gonads
→ For primary and secondary sexual
development
sex hormones
→ Released by kidneys
→ Ca binding proteins
→ For Ca reabsorption in intestine
Vitamin D
Receives signals in the cytoplasm which
goes inside the nucleus to elicit a
response
cytoplasmic/ gated receptor
Receptor found inside nucleus
Signal goes directly inside the nucleus
and then attaches to receptor
nuclear receptor
Lipophobic, lipid insoluble ligands
→ Release secondary messengers
→ Secondary messengers are needed to elicit a response
plasma membrane receptors
Also known as ligand-gated ion channels or
ionotropic receptors.
Controls influx and efflux of ions that leads to a change in membrane potential causing
depolarization and hyperpolarization.
ion channels
Involves transducing a chemical signal into an
electrical signal, which elicits a response
e.g. ryanodine receptors (located in the
sarcoplasmic reticulum of skeletal muscle), gets activated by Ca2+ (or by caffeine, ATP, or
metabolites of arachidonic acid) to release Ca2+ from SR → facilitates muscle contraction
ligand-gated channel linked signal
- Function: Bind guanine nucleotides GDP (inactive) and GTP (active)
- regulate activity of other proteins
G protein coupled receptor
what are the two types of GPCR?
monomeric and heterotrimeric
Play a central role in many enzyme linked receptor pathways [Berne, et al, 2018]
▪ Also functions in the regulation of gene expression and cell proliferation, differentiation, and survival [Berne, et
al, 2018]
monomeric
- Consists of α,β,ɣ subunits
Regulates the activity of other protein (enzymes & ion channels).
● The interaction between receptor and target protein is mediated by heterotrimeric G protein (composed of 𝛼,𝛽,𝛾 subunits)
heterotrimeric
this is the site of ligand binding
extracellular domain
Attached heterotrimeric
complexes
intracellular domain
without ligand the G protein is __________
inactive
with ligand, G protein is______________
activated
What are the GPCRs target effectors?
→ Ion channels
→ Cyclic Adenosine Monophosphate (cAMP)
→ Phospholipase C (PLC)
→ Cyclic Guanosine Monophosphate (cGMP)
→ α goes to adenylyl cyclase
→ cAMP signal pathway
→ cAMP and cGMP
adenylyl cyclase
→ Phospatidyl-inositol signal pathway
phospholipase c
releaser of Ca2+ on the ER
IP3
activates protein kinase C (for cellular growth and proliferation)
Diacylglycerol (DAG)
what are the enzyme-linked/ catalytic receptor?
guanylyl cyclase
threonine/ serine kinase
tyrosine kinase
tyrosine kinase- associated
what are the cytokines and ligands of guanylate cyclase?
atrial natriuretic peptide (ANP) and Nitric Oxide
What are the cytokines and ligands of tyrosine kinase
EGF, platelet-derived
growth factor (PDGF), and
insulin
→ ANP or NO + GC receptor > metabolizes GTP to cGMP > cGMP activates protein kinase G > PKG phosphorylates protein on specific serine and threonine residues
guanylate cyclase receptor
what are the two types of guanylate cyclase receptor?
transmembrane guanylate cyclase receptor and soluble guanylate cyclase receptor
− Activated by atrial natriuretic peptide
− Present in the cell membrane
− Result: Inhibits sodium and water reabsorption in kidney.
transmembrane guanylate cyclase receptor
− Activated by nitric oxide (vasodilator).
− Present inside the cell
− Result: smooth muscle relaxation
Soluble guanylate cyclase receptor
Involved in the activation of inositol-1,4,5-
triphosphate (IP3) pathway.
Signal binds to GPCR > GDP is displaced by GTP > 𝛼 subunit dissociate and attach to PLC >
hydrolysis of PIP2 producing Diacylglycerol
(DAG) and IP3.
- Physiological significance: Ca 2+ promotes
muscle contraction.
Phospholipase C
- is structurally composed of two regulatory
and two catalytic subunits. When the produced cAMP bind to the two regulatory subunit, the two catalytic subunit will dissociate and will now function as the active protein kinase. - as a member of the transferase family of
enzymes catalyzes the transfer of phosphate
groups or phosphorylation reaction
Phosphokinase A (PKA)
Stimulus involved is light (phototransduction).
cyclic GMP
- absorbs light in the rods of eyes.
rhodopsin
Once rhodopsin absorbs light it activates G
protein ____________ via alpha T which then
activates cGMP phosphodiesterase
transducin
cell differentiation, proliferation & survival;
induces cell division/mitosis;
prevents/encourages cell growth in cell cycle
Ligand-dependent ; commonly triggered by
hormones (e.g. estradiol) and growth factors
mitogen-activated protein kinase (MAPK) pathway
produces lymphokines modifying host
organism to improve immunity
T cells
producing immunoglobulins/antibodies
B cells
- activates AKT/Protein Kinase B
- Associated with the Go phase of mitosis (when the pathway is less active) and long term potentiation among neural stem cells
- Overactivity of this pathway reduces apoptotic activity of cells which allow proliferation
P13K (Phosphoinositide-3-Kinase)
Tyrosine-associated Kinase receptor
Involved in immunity, cell division and death as well as tumor formation
JAK/ STAT pathway
