chap 3- intercellular communications (b1- foundation) Flashcards
cells stick together and stay organized in tissues by what 3 methods?
- CAMs (cell adhesion molecules)
- Extracellular Matrix (ECM)
- Specialized Cell Junctions
functions of the plasma membrane
- Mechanical barrier
- Selectively permeable to ensure specific intracellular composition
- Participates in joining of cells to form tissues and organs
- Enables a cell to respond to changes or signals in the cell’s environment
3 functions of CAMs (cell adhesion molecules)
CAMs hold tissue together: help cells stick to each other, forming tissues & keeping them intact
- without CAMs, tissues would just fall apart
1. Role in embryonic development: Cams work like “ID tags” (made of proteins w/ carbs attached) on cell surface to help cells find & attach to the right partners to form tissues and organs
2. Role in Inflammation & wound healing: CAMs help immune cells stick to blood vessel walls & move to the site of inflammation or injury
- helps speed up healing by allowing right cells to reach the wound quickly
3. Metastasis of Tumors: normally CAMs control tissue growth by keeping cells attached
- if cells have abnormal CHO (carb) markers, lose their proper connections and break out to go to other parts of the body
4 types of CAMs
1. Integrins: transmembrane proteins, connect extracellular matrix (ECM) to intracellular cytoskeleton
- help in cell movement, tissue repair, and immune responses
2. Cadherins: calcium (Ca²⁺)-dependent peripheral proteins
- hold adjacent cells together by forming strong connections (kinda look like hooks)
3. Selectins: single-chain transmembrane glycoproteins (proteins with sugars attached).
- bind to sugar molecules in the extracellular fluid (ECF).
- 3 types: P, E, & L
4. Immunoglobulin (IgG) Superfamily: structurally similar to antibodies (look like circles w/ receptors) but help in cell adhesion rather than immune defense
- ICAMs help white blood cells attach to blood vessels to move (leukocyte endothelial transmigration)
what type of cells secrete ECM (extracellular matrix) components?
fibroblasts
4 structural proteins in the ECM
1. Collagen: non-elastic but flexible fibers that are responsible for tensile strength (resistance to stretching and pulling forces).
- Most abundant protein in body,
- found in bones, skin, tendons, cartilage, and connective tissues
- deficiency leads to SCURVY
2. Elastin: rubbery protein that allows tissues to stretch and recoil without damage.
- found in tissues that need flexibility, such as
walls of arteries and veins, lungs, skin
(loss of elastin over time contributes to skin aging and wrinkles)
3. Fibronectin: promotes cell adhesion by helping cells attach to ECM, plays crucial role in wound healing and tissue repiar
- defects in fibronectin = cancer b/c cells break free and metastasize
4. Laminins: large cross-shaped protein molecules w/ multiple receptor domains for binding w CAMs
- found in basement membranes which support epithelial cells (cells that form skin & organ linings)
- work closely with interns to anchor cells to the ECM
deficiency of collagen
leads to SCURVY – a disease caused by vitamin C deficiency, which prevents proper collagen formation, leading to weak connective tissues, fragile skin, and bleeding gums.
3 types of specialized junctions that hold cells in tissues together
- Occluding Junctions (aka tight junctions/zona occludens)
- Communicating Junctions (aka Gap junctions)
- Adhering Junctions (aka Anchoring Junctions)
specialized cell junctions: occluding junctions/tight junctions/zona occludens (structure + function)
function: prevent leakage of molecules between cells (act as a seal), maintains diff composition of proteins & lipids, maintains cell polarity, forms selectively permeable barrier for small molecules but total barrier for large molecules
found in epithelial tissues, like the intestines, stomach, and blood-brain barrier (where leakages would be harmful - like acids leaking and stuff)
structure: tight junctions form a continuous belt (that has 2 halves) around cells, sealing spaces between them
- 1 half belongs to one cell and the other to the other cell and they come together and fuse tightly in the middle (not the whole cell is glued together) - called the kiss site
- junction made of claudins and occludins (proteins that form a tight seal).
tight junction functions: blood-brain barrier
These junctions in the brain capillaries forms the blood brain barrier, which prevent the entrance of many substances from capillary blood into brain tissues
Only lipid soluble substances like drugs and steroid hormones can pass through the blood brain barrier
specialized cell junctions: function of communicating/gap junctions (also called nexus)
allow direct communication between adjacent cells by permitting the exchange of ions, nutrients, and small molecules (glucose, amino acids, ions like Na+, K+, Ca2+, and chemical messengers)
normally space between cells is ~25nm, but in gap junctions, is reduced to just 3 nm
important in heart and nervous system where signals need to go fast
- also in basal part of epithelial cells in intestinal mucosa
chemical synapse is an example of communicating junction
specialized cell junctions: structure of communicating/gap junctions
- each channel has 2 halves, belonging to each adjacent cell
- each half of channel (called connexon) is surrounded by 6 subunits of proteins called connexins
- connexins determine permeability/selectivity of gap junction
opening/closing of gap junctions is controlled by what factors?
Intracellular Ca²⁺ levels (high Ca²⁺ can close gap junctions to prevent damage from spreading)
pH changes (low pH may close the junctions)
Electrical potential differences between cells
Hormones and neurotransmitters affecting cell signaling
specialized cell junctions: adhering junctions
adhering junctions: link cells to each other or to the extracellular matrix, providing mechanical strength and structural integrity
2 types → Desmosomes and Hemidesmosomes
Desmosomes → connect adjacent cells
- main protein is cadherins (which are calcium dependent)
- located in skin, heart, uterus
Hemidesmosomes→ connect cells to the basement membrane
- main protein is integrins
- located in epithelial cells (skin, cornea, mucosa)
adhering junctions: desmosomes
connect adjacent but non-touching cells, providing strong adhesion
-most abundant in tissues exposed to mechanical stress, such as: skin, uterus, and heart muscle
consist of: plaques just inside cell membrane that serve as anchor points for intermediate filaments that are in the middle connecting the desmosomes on opposite sides → strong, flexible network
- plaques have cadherins that connect them
Desmosome defects leads to what disease
Pemphigus vulgaris & pemphigus foliaceus
- layers of skin pull apart and allow abnormal movements of fluid within skin, resulting in blisters and other tissue damage
- caused by autoimmune disease where antibodies attack desmosomal cadherins, weaning the cell-cell adhesion
adhering junctions: hemidesmosomes
similar to desmosomes, but they attach cells to the basal lamina (basement membrane) instead of other cells to provide stability to tissues
consist of integrins (transmembrane proteins so they can connect the cell to the basement membrane)
- also connected intracellularly (within cell) to intermediate filaments to provide structural support and anchor cell to ECM
Adhering junctions (desmosomes) are most abundant in which of the following tissues?
Tissues subjected to mechanical stress, like skin and heart muscle
classify modes of cell signaling + give their examples
Direct signaling: contact dependent
- 2 cells must physically touch for communication to happen
- Gap Junctions
- Tunnelling nanotubules (TNTs- for larger cargo, longer distances)
- Direct link up of surface markers
Indirect Intracellular Communication: By chemical messengers
- cells release chemical messengers that travel to other cells and bind to receptors there
- Autocrine
- Paracrine
- Endocrine
- Neurotransmitters
- Neuroendocrine
- Cytokines
indirect communication: autocrine signaling + example
same cell sends & receives the signal
- cell secretes a chemical messenger that then binds to a receptor on the same cell
example: interleukin-1 in monocytes (type of leukocyte)
- when monocyte stimulated = produces interleukin-1
- same interleukin-1 binds back to receptors on the monocyte itself
- helps cell respond stronger and regulate its own activity
indirect communication: paracrine + example
cell sends a chemical messenger to nearby cells (not to itself or far-away cells)
- works in the local environment
- signal is usually short-lived because it’s broken down by enzymes nearby
example: histamine
- when injury/allergy = cells release histamine
- causes nearby blood vessels to dilate (open up), causing swelling/redness
Purpose: Local coordination like healing or inflammation
indirect communication: endocrine + examples
cells (usually in glands) release hormones into the blood
- hormone travels long distances through the blood
- only target cells (with the right receptors) respond to the hormone
examples:
- Insulin (from pancreas to body cells to reduce blood sugar)
- Growth hormone (from pituitary to bones/muscles for growth)
Purpose: Long-range regulation — like growth, metabolism, reproduction
indirect communication: neurotransmitter/neuronal signaling + examples
neurons (nerve cells) release neurotransmitters from their axon terminals into synapse
- these chemicals cross the gap to reach nearby target cells (another neuron, muscle, or gland).
Very fast and short-range
examples:
- Acetylcholine – for muscle movement
- Dopamine – for mood and pleasure
- Norepinephrine, Glycine, etc
Purpose: Rapid communication, like muscle contraction or brain signaling
indirect communication: neuroendocrine signaling (neurohormones) + examples
neurons that release hormones instead of neurotransmitters
- these special neurons are called neurosecretory neurons
- hormones are released into blood, so the signal can travel far
examples:
- Vasopressin (ADH) – controls water balance in kidneys
- Adrenaline – prepares body for “fight or flight”
Purpose: Combines the speed of neurons with the long-distance effect of hormones
indirect communication: cytokines + examples
peptides (small proteins) that any cell can release, especially immune cells
- can act in autocrine, paracrine, or endocrine ways depending on the situation
- help regulate immune responses, inflammation, and cell growth
examples:
- Interleukins – regulate immune cell behavior
- Lymphokines – from lymphocytes
- Adipokines – released from fat (adipose) tissue
Purpose: Versatile signals used heavily in the immune system and inflammation
direct signaling: gap junctions
tiny tunnels/pores that directly connect the insides of two neighboring cells
- pores made of proteins called connexins
- ions and small molecules (like calcium, glucose, or second messengers) move directly from one cell to another
direct signaling: tunneling nano tubules (TNTs)
long, thin tubes made from the cell’s cytoskeleton that connect cells over longer distances
- larger than gap junctions, allow cells to pass larger cargo, like proteins, organelles (like mitochondria), even viruses
- are temporary structures — cells build them when needed
extra info:
- found in immune cells, cancer cells, neurons, etc.
- can be used for both normal communication and sometimes spreading infections (like viruses or misfolded proteins in neurodegenerative diseases)
direct signaling: direct link-up of surface markers
cells communicate by physically recognizing each other’s surface proteins — like shaking hands to recognize someone
- one cell has specific protein (ligand) on its surface
- other cell has a receptor that fits that ligand
- when bind, triggers a response inside the cells
example:
Immune T cells recognizing infected or cancer cells:
The infected cell shows a “bad” marker on its surface.
The T cell’s receptor recognizes it and kills that specific cell.
This ensures that only undesirable cells are destroyed, not healthy ones.
how do receptors relay signals via intracellular signaling pathways?
signaling molecule (eg. hormone) binds to receptor outside cell → conformational change in receptor that activates it → starts message relay inside cell → second messengers activated (intracellular signaling molecules) that spread the signal inside cell (like cAMP, Ca2+) → signal amplificiation (signaling cascade that is a chain of events that amplifies the signal) → eventually, signal reaches target proteins that are activated and lead to cell’s response
plasma membrane receptors vs intracellular receptors + classifications
plasma membrane receptors: located on outside surface of cell membrane, detect water soluble (lipid-insoluble) messengers
- messengers cannot cross membrane so need receptors on surface
- receptors that function as:
- ligand gated ion channels
- enzymes
- bound to and activate cytoplasmic enzymes
- receptors that activate G proteins
intracellular receptors: located inside cell (either cytoplasm or nucleus), detect lipid-soluble messengers like steroid hormones
- cytoplasmic receptors
- nuclear receptors
further types of plasma membrane receptors
-
Ligand-gated ion channels:
- when signal binds, channel opens or closes
- ex. nicotinic ACh receptors - receptors that function as enzymes (usually tyrosine kinase receptors)
- receptor is enzyme or becomes 1 when activated
- when signal binds, receptors activates enzyme activity inside cell
- ex. insulin receptor that activates kinase to increase glucose uptake
- growth factors such as nerve growth factor & epidermal growth factor (help regulate cell growth & division) -
Enzyme-linked receptors/Catalytic receptors: receptors that are bound to & activate cytoplasmic enzymes
- receptor itself isn’t enzyme but connected to enzyme inside cell
- signals bonds = receptors activates that enzyme
- ex. JAK/STAT pathway -
G-protein coupled receptors: type of membrane receptor that initiates a # of metabolic steps to modulate cell activity
- ex. adrenergic receptors
further classification of intracellular receptors
-
nuclear receptors: already in nucleus
- bind messenger directly & act as transcription factors
- turn genes on or off
- ex. thyroid hormone binds nuclear receptor -
cytoplasmic receptors: found in cytoplasm, signal molecule binds and complex moves into nucleus = changes gene expression
- ex. cortisol binds cytoplasmic receptors
down regulation & up regulation (mechanisms of receptor regulation)
down regulation: cell reduces its sensitivity to signal (protection from overstimulation if too much signal), two ways:
- internalization (receptor-mediated endocytosis): receptors on membrane pulled into cell by endocytosis so fewer receptors left on cell surface
-
desensitization (chemical modification): receptors stays on membrane, but is chemically changed (eg. phosphorylation)
- makes it inactive or less responsive
- like turning off switch without removing it
upregulation: cell becomes more sensitive to a signal
- b/c less of a signal available so cell increases # of receptors on surface
example of enzyme linked receptors: the JAK/STAT pathway
binding of ligand to target cell → activates enzyme janus kinase (JAK) attached to cytosolic side of receptor → JAK phosphorylates STAT (signal transducers & activators of transcription) within cytosol → phosphorylated STAT moves to nucleus → turns on gene transcription → synthesis of new proteins that carry out cellular response
how is signal transduction turned off?
protein phosphatases remove phosphate groups from designated proteins
- quickly shut off signal transduction pathway if its signal molecule is no longer bound at the cell surface
chronic myeloid leukemia (CML)
cancer of the bone marrow where blood cells are made - problem in white blood cells formation & control (grow too much & don’t mature properly)
caused by:
1. unregulated tyrosine kinase activity: mutation causes enzyme tyrosine kinase to always be “on” (phosphorylated) when it shouldn’t be = keeps phosphorylating signaling proteins
- increased expression of growth regulatory genes: constant signaling = genes that control growth are overactive = leads to too many white blood cells being made even when body doesn’t need them
