GBS709 Week 1

list membrane bound organelles and non-membrane bound***

membrane bound: plasma membrane, nucleus, endoplasmic reticulum, golgi apparatus, lysosomes, endosomes, peroxisomes, mitochondria

non-membrane bound: ribosomes, proteasomes, cytoskeleton elements, centrioles, basal bodies, cilia, flagella

what is dis?

fluid mosaic model, contains lipid rafts which serve as “signaling platforms”

glycerophospholipid

main phospholipid in most animal cell membranes

lipid composition

polar, hydrophilic head: choline, phosphate

nonpolar hydrophobic tails: 3C glycerol backbone, hydrocarbon tails with double bonds

Lipids that form a bimolecular leaflet are ______?

amphipathic meaning they contain hydrophobic and hydrophilic components

cholesterol

rigid, in lipid bilayer

cell membranes are composed of

proteins and lipids

3 major lipids in cell membrane

phospholipids, glycolipids, cholesterol

4 major phospholipids

phosphatidylethanolamine, phosphatidylserine (net negative), phosphatidylcholine, sphingomyelin, sphingosine

2 major protein groups in cell membrane

Integral: transmembrane, multipass

Peripheral: extracellular, cytosolic

6 functions of cell membranes

1. maintains structural integrity

2. controls movement of substances in and out

3. regulates cell-cell interactions

4. serves as recognition board via receptors

5. establishes transport system for specific molecules

6. transduces extracellular physical and chemical signals into intracellular events

4 kinds of membrane proteins

channel proteins, pump + carrier proteins, surface receptors, linkers + structural prteins

channel proteins + 3 examples

allow passage of ion or charge; voltage-gated, ligand-gated, mechanically-gated

pumps and carrier proteins + 3 examples

bind and transport ions and molecules; Na⁺- K⁺ pump, Ca⁺⁺ pumps, glucose transporter

surface receptors + 2 examples

• bind to ligand to elicit cellular response

• involved in receptor-mediated endocytosis

• signaling molecules which are or are associated with kinases (enzymes that phosphorylate)

• coupled to G-proteins

ex) cytokine and steroid receptors

linkers and structural proteins

cell-cell attachment; cell-matrix attachment, scaffolds for cytoskeleton

Histogenesis***

formation or development of tissues, begins at gastrulation (day 15/16 in early embryogenesis)

Gastrulation***

process where 3 germ layers are generated and placed in proper position in embryo:

• ectoderm externally

• mesoderm in between

• endoderm internally

4 essential processes for generation of multicellular organism***

cell proliferation, specialization, interaction, and movement

4 tissue types

epithelial, connective, muscle, nerve

epithelial tissue/epithelium + 2 types

• sheet covering free surfaces, creates border between environment and organ, controls movement of substances

• cells collectively bound and sit on basement membrane

• basis for gland formation

• avascular; no blood vessels

• polarized structure and function

• derived from all 3 germ layers (ectoderm, mesoderm, endoderm)

endothelium vs epidermis***

endothelium - epithelium lining blood vessels, epidermis - epithelium of skin

basement membrane

attaches epithelium to underlying connective tissue by specialized cell junctions, PAS-positive layer is visible by light microscopy

7 functions of epithelium ***

1. protection: epidermis

2. absorption: digestive tract

3. secretion: secretory cells within glands are derived from epithelial tissue

4. excretory: kidneys

5. lubrication: pleura, pericardium and peritoneum; allows movement of organs within cavities.

6. sensory: many specialized sensory cells are derived from epithelium such as taste buds, retinal pigmented epithelia

7. reproduction: sperm are modified epithelial cells transformed into spermatozoa

2 domains of polarized cell

apical and basolateral, results in polarization of cell in epithelium

Basal Lamina

• secreted by epithelial cells, interface between epithelia and underlying supportive tissues

• permits movement of nutrients to epithelial cells from blood, and movement of metabolites towards blood

• binds and concentrates growth factors in cell growth and proliferation

• influences cell metabolism and cell-to-cell interactions/signaling

• part of basement membrane

2 types of epithelial glands

• Exocrine: organized into specific units that secrete into a tubular network of ducts

• Endocrine: cells that secrete directly into blood stream

all glands are derived from epithelial tissue

Epithelium Renewal

• variable; fast (intestinal epithelium replaced weekly) or slow (large glands)

• in stratified layers, mitosis only occurs in cells at basal layer

• rapid repair and replacement of damaged cells

carcinomas

tumor of epithelial origin. adenocarcinomas are tumors of glandular epithelial

Connective Tissue + know diagram

• mesodermal origin, tissue-specific ECM consisting of fibers and ground substance (clear, colorless gel-like fluid) with blood vessels and nerves (except cartilage)

• forms a continuum with epithelial, muscle and nervous tissues

• stores fat as adipose tissue

• facilitates signaling; cell membrane receptors bind matrix molecules to control adhesion, differentiation, cell cycle

• defense, protection, wound healing, tissue repair

ex: connective tissue proper (loose or dense), cartilage, bone, adipose tissue, blood, mesenchymal connective tissue (embryonic, undifferentiated)

2 examples of connective tissue

parenchyma: perform major function of that organ (hepatocytes in liver, alveolar cells in lung)

stroma: connects/supports other elements of tissue

2 types of connective tissues ***

connective tissue proper (loose and dense w/ irregular and regular) and specialized connective tissue (cartilage, bone. blood, adipose)

2 types of cells in connective tissue

resident (fibroblasts, adipocytes, pericytes, mast, tissue macrophages, stem cells) and transient (white blood cells)

Fibroblasts

principal cell of connective tissue, synthesis of ECM fibers (collagen, elastic, reticular) and ground substance, rarely divide but mitosis resumes during wound healing, not terminally differentiated

Adipocytes

• energy storage, insulation, cushioning of organs and secretion of hormones

• large cells, up to ~100um

• lipid mass is not membrane bound

• white (unilocular) or brown (multilocular)

• hormones involved in weight control

• leptin and insulin

Leptin

produced exclusively by adipocytes, reduce appetite (obese people have high levels and are resistant to leptin activity)

insulin

stimulates uptake and synthesis of triglycerides

blood

• specialized connective tissue, develop in bone marrow and enter circulation fully formed

• adults have ~5-6 liters

• red blood cells and platelets generally remain in vascular system

• white blood cells can leave circulation and enter interstitial compartments, only lymphocytes can return to vascular compartment

6 functions of blood ***

• transports: gases (O₂, CO₂), nutrients, hormones, chemical signals

• buffer system: maintains pH at 7.4

• temperature control: conjunction with blood vessels that dilate or constrict to release or conserve heat

• removal: cellular and metabolic wastes

• immune functions: defense against infection

• coagulation functions: prevent massive blood loss

hematocrit of human blood

volume of packed erythrocytes in a sample of blood (cells 45%, plasma 55%, leukocytes and platelets 1%). a normal hematocrit is 39-50% in males and 35-45% in females

plasma

fluid of blood, 55% of total blood volume, liquid extracellular material (ECM). Plasma w/o coagulation is called serum

7 key components of blood (may not be important, idk)

• albumin (most abundant protein in plasma)

• immunoglobulins (IgA, IgG, IgM, IgE, IgD), Complement system

• lipoproteins; chylomicrons, VLDL, IDL,LDL (‘bad cholesterol”), HDL

• haptoglobin, plasminogen, transferrin, and transport proteins.

• fibrinogen and other clotting molecules

• hormones (soluble or protein bound)

• electrolytes, nutrients, gases, etc.

blood composition ***

• plasma (water, protein, solutes)

• erythrocytes

• buffy coat (platelets and leukocytes)

Cartilage

• specialized connective tissue, part of skeletal system

• provide flexible support (bone rigid template for bone formation)

• in respiratory system, joints, external ear

• avascular, no nerves or lymphatics

• composed of cells (chondroblasts, chondrocytes) + matrix (fibers: collagen II, elastic fibers and ground substance: proteoglycans and glycosaminoglycans/GAGs)

• shock absorber: w/ pressure, water forced out of tissue to absorb pressure, w/o pressure, water rebinds PG aggregate and tissue returns to original size

3 types of cartilage

• Hyaline: most common arrangement – nasal septum, joint surface, ribs

• Elastic: like hyaline but enriched with elastic fibers – ear, larynx

• Fibrocartilage: rows of chondrocytes with increased fibrous matrix – intervertebral disks, tendon/ligament attachment

bone

• calcium store (also Mg⁺⁺ and Na⁺), hematopoiesis (marrow)

• alive, dynamic and continually remodeling

• highly vascularized (compared to cartilage)

• composed of cells and matrix (inorganic and organic)

• organic is fibers: type I collagen, highly organized and ground substance: little, some PG as cartilage

• inorganic: 50% of matrix is calcium phosphate complexes, rigid

3 types primary cells in bone ***

• Osteoblasts: immature, synthesize and secrete osteoid which becomes mineralized to give bone; do not divide.

• Osteocytes: surrounded by and maintain matrix; do not divide.

• Osteoclasts: large multinucleated macrophages, from monocyte lineage, remodel bone by resorbing bone matrix.

2 types mature bone ***

• Cancellous (spongy): trabeculae (fine irregular plates), inside long bones (marrow), gives strength without weight

• Compact: highly ordered, outer and inner circumferential lamellae, contains Haversian systems (osteons)

muscle

• contractile cells that are responsible for movement.

• contraction is dependent on interactions between actin and myosin (rearrangement of fibers will differ)

• voluntary/involuntary; striated or nonstriated

3 types muscles

• Skeletal: striated/voluntary, attached to bone (bicep, oblique), few places not bundled (tongue, esophagus)

• Cardiac: striated/involuntary, wall of heart and base of veins that empty into heart.

• Smooth: non-striated/involuntary, lining blood vessels, visceral organs

Muscle Tissue

• derived from mesoderm

• sarcolemma (cell membrane) vs sarcoplasm (cytoplasm)

• sarcoplasmic reticulum (SR) is modified ER.

• contraction of muscle depends on interaction of actin and myosin and is regulated by cellular calcium levels

muscle tissue cells

• length up to ~30 cm; diameter 10-100 um

• multinucleated syncytium (muscle fiber)

• continuous with tendon or other dense connective tissue

• highly vascularized

skeletal muscle tissue

• bundles of long, cylindrical multinucleated cells w/ cross striations

• contraction thro thin actin and thick myosin filaments

• controlled by somatic nervous system

• attached to bone

• visceral striated muscle (oral cavity, larynx, pharynx, upper esophagus, anal region)

• extraocular muscles in eye

3 types of connective tissue associated with muscle tissue ****

1. epimysium: dense connective tissue surrounding entire muscle.

2. perimysium: connective tissue surrounding bundles of muscle fibers

3. endomysium: delicate connective tissue surrounding each muscle fiber

Sarcomere

extends from Z-line to Z-line, smallest repetitive subunit of contractile unit

Arrangement of Thick and Thin Filaments

have an appreciate for this image

Neuromuscular Junction

this type of junction is only found in voluntary muscle

Cardiac Muscle Tissue

tightly knit bundles of cells, produces a characteristic wave of contraction that leads to a wringing out of heart ventricles

Cardiac Muscle Cells ***

• 15 um in diameter, 85-100 um long

• cross-striated banding pattern and sarcomere arrangement/function same as skeletal muscle

• each cell has 1-2 central nuclei, covered by sheath of endomysial connective tissue w/ capillary network w/ no perimysium or epimysium

• instead of forming syncytial cells like skeletal muscles, they branch and form complex junctions between their processes and neighboring cells

• intercalated disks: dark-staining transverse lines that cross chains of cardiac cells at irregular intervals.

• cardiac muscle contraction passed from cell to cell via communication through gap junctions.

smooth muscle tissue

• elongated, nonstriated, fusiform cells (largest at midpoint and tapered at ends)

• cells enclosed by basal lamina and network of reticular fibers; both combine forces generated by smooth muscle fiber into concerted action

• smooth muscle contraction is passed from cell to cell via communication through gap junctions.

• found lining GI tract (esophagus, stomach, intestines), respiratory tract, uterus, bladder and urethra, lining blood vessels, dermis of skin (arrector pili muscles)

• tight packaging of tissue achieved by lining up cells with narrow parts of some cells against broad parts of neighboring cells

• contain dense bodies for attachment of filaments and propagation of contraction

nervous system

• receives, transmits and integrates information from outside and inside body to control and coordinate activities in body

• Central Nervous System (CNS) and Peripheral Nervous System (PNS)

Central Nervous System (CNS)

brain, spinal cord, eyeballs

Peripheral Nervous System (PNS)

• peripheral (cranial and spinal) nerves and ganglia (aggregations of nerve cell bodies, somatic/sensory and autonomic)

• somatic and autonomic (parasympathetic division (rest and digest), sympathetic division (fight or flight), enteric division (GI function))

Neurons (nerve cells)

nerve cells specialized to transmit electrical impulses, made of axon, cell body and dendrites; morphology (uni-, bi-, multi-polar), function (integrative, sensory, motor)

11 organ systems

1. gastrointestinal (digestive)

2. musculoskeletal

3. integumentary (skin)

4. blood and lymphatic

5. endocrine

6. nervous

7. skeletal

8. reproductive

9. pulmonary

10. urinary

11. cardiovascular

epithelial cells

polarized, apical and basal, consist of basement membrane and stromal matrix

cell-cell junctions

tight, adherens, desmosome, gap

tight junction

• seals gap between epithelial cells

• restricts flow of solutes, water, and movement of plasma membrane proteins

• this creates apical and basolateral domains with different surface proteins

• mediated by claudins and occludins/tricellulins

tight epithelium vs endothelium

tight epithelium has a lot of tight junctions such as the collecting duct in kidney. tight endothelium (blood-brain barrier)

apical vs basal surfaces

apical: lumen of intestine. basal: supportive connecting tissue and muscle

adherens junction

connects actin filament bundle in cells, mediated by cadherins (E-cadherin in epithelial cells)

E-cadherins

• homodimers, mediates epithelial cells in adheren junctions

• E-cadherins and cell association regulated by Ca⁺⁺ binding

• this causes E-cadherin to extend out like a rod, enabling contact with other cell

desmosome

dense plaques, connects intermediate filaments in cells, mediated by desmoglein (a type of cadherin), requires Ca⁺⁺

gap junction

allows passage of small water-soluble molecules from cell to cell

cell-matrix junctions

actin-linked cell-matrix, hemidesmosome

actin-linked cell-matrix junctions

anchors actin filaments in cell to extracellular matrix, focal adhesion

hemidesmosome

anchors intermediate filaments in a cell to extracellular matrix

Cell-cell and cell-matrix junctions are critical for_____?

maintaining cell polarity!

why is apical-basal polarity important?

critical for normal cell function, locomotion and formation of immune synapse, polarization of epithelial cells also acts as a tumor suppressor

what does loss of polarity (loss of cell-cell or cell-matrix adhesion) cause?

• de-differentiation

• epithelial to mesenchymal transition

• increased migration/invasion

How do you get different proteins on the apical surface versus the basal surface?

cargo sorting by the trans-golgi network (TGN) - specific coat proteins direct TGN vesicles to targets

6 steps as to how polarity causes cell locomotion

1. direction of movement

2. front protrusion: protrusion forms at leading edge w/ F-actin polymerization by Rac, Cdc42, Rho (G-proteins that organize cytoskeleton)

3. front adhesion: formation of new adhesion

4. cell-body translocation: actomyosin contraction allows cell body to translate

5. tail deadhesion: adhesion at trailing end disintegrates and F-actin depolymerizes

6. tail retraction

how does polarity form the immune synapse?

Antigen presenting cells (APC) or tumor cell causes T cell to become polarized after binding

cytoskeletal filaments + 3 types

• polymers composed of non-covalently-bound monomers

• interaction between two monomers is weak and noncovalent, stabilized by multiple bonds

• weak bonds between individual monomers allows filament polymerization to be dynamic

actin filaments (microfilaments), intermediate filaments, microtubules

actin filaments

• determine cell shape, and regulate cell locomotion

• 2 protofilaments that twist around in a right-handed helix, POLAR

• can combine to form actin bundles (stress fibers), requires accessory G-proteins

4 G-proteins involved in actin bundle formation

quiescent cells, Rho activation, Rac activation, Cdc42 activation

actin monomer

• globular structure, ATP cap

• have ATP bound because more ATP than ADP in cell

• can hydrolyze ATP

intermediate filaments

• rope-like, provide mechanical stability and serve as scaffolds for signaling molecules

• stabilize epithelial and endothelial cell monolayers in the presence of shear stresses

• NO POLARITY (ends are symmetrical)

• regulation of polymerization appears to involve phosphorylation

• can withstand greater deformation and force without breaking compared to other cytoskeleton filaments (MTs or actin)

intermediate filaments composition

• Keratins (variant) – epithelial cells

• Vimentin – fibroblasts, endothelial cells, leukocytes, contribute to mechanical stability of lymphocytes

• Desmin – muscle cells

• Glial fibrillary acidic protein – glia

• Lamins – ubiquitously expressed, localized to nucleus

how are intermediate filaments made?

1. a-helical region in monomer

2. coiled-coil dimer

3. staggered tetramer of 2 coiled-coil dimers

4. 2 tetramers packed together

5. 8 tetramers twisted into rope filament

microtubules

• determine positions of membrane-enclosed organelles, and direct chromosomal separation during mitosis

• made of α/β tubulin dimers w/ GTP cap, have ring of 13 protofilaments w/ + and - ends

• originate in centrosome, lie just under the plasma membrane to provide support

how does the polar structure of actin and microtubules contribute to polymerization? also what happens if the GTP cap is lost?

• head and tail ends of polymer are different w/ ATP (actin) or GTP (microtubules) on one end, and ADP/GDP at the other

• + end: fastest polymerization

• - end: slowest polymerization

• ATP or GTP “caps” promote assembly

• ADP/GDP ends tend to disassemble

• GTP cap forces GDP-bound monomers to stay in a linear conformation

• filament disassembles if cap is lost

DYNAMIC INSTABILITY

minor, temporary fluctuations in rates of assembly/disassembly, characteristic of microtubule polymerization.

TREADMILLING

rate of assembly at plus end exactly matches the rate of disassembly at the minus end

ARP-mediated nucleation of actin filaments

• on inner leaflet of plasma membrane – cell locomotion

• on side of actin filament – creates web-like structure

Nucleation of microtubules

γ-tubulin forms a ring-like structure that serves as nucleating site for microtubules

what do accessory proteins that modulate filament polymerization or stability do exactly? + 3 examples

• regulate nucleation (proteins that help/inhibit recruitment of monomers to nucleation site)

• stabilize/destabilize pre-existing filaments by binding to sides/ends of polymer

filament-cleaving/bundling proteins, actin-bundling, microtubule-bundling

Filament bundling proteins

Actin bundling proteins, can link actin with α-actin, fimbrin, and filam

actin filaments linked to α-actin

• creates a contractile bundle: loose packaging allows myosin-II to enter bundle, stress fibers

• stress fibers

actin filaments linked to fimbrin

• causes parallel bundle: tight packaging prevents mysoin-II from entering bundle

• gel-like network, cell cortex

• bundles within microvilli