Membrane junctions Flashcards by Ken Valdellana

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

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this is the functional units of gap junctions

connexon

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this is the protein subunits of gap junctions

connexins

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 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

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 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

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what are the membrane junctions?

gap junctions, tight junctions, desmosomes

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 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

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ability to coordinate cellular
activities and function

cell signaling

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what are the cellular responses?

 Movement
 Apoptosis
 Synthesis
 Differentiation
 Metabolism
 Secretion
 Multiplication
 No response (also a response)

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TYPES OF INTRACELLULAR SIGNALLING

 Electrical
 Cell-cell communication
 Chemical

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 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

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 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

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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

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 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

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what are the 3 types of chemical signaling?

autocrine
paracrine
endocrine

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→ 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

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→ 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

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→ 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

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what are the cellular receptors?

intracellular receptors and plasma membrane receptors

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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

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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

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what are the steroid receptors?

cortisol
sex hormones
vitamin D
cytoplasmic/ gated receptor
nuclear receptor

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→ Released by adrenal cortex
→ For gluconeogenesis

cortisol

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→ Released by gonads
→ For primary and secondary sexual
development

sex hormones

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→ 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