Cytoskeleton

What is dynamic instability

sudden conversion from growth to shrinkage and vice verse as long as there is a uniform free subunit concentration 

What is keratin

in hair/nails 

• Made of intermediate filaments (most common type) 

• Anchor to desmosomes/hemidesmosomes 

• Alterations lead to unusual blistering diseases 

What is intermediate filament (simple)

ropelike fibers made of intermediate filament proteins 

Several types: 

• Provides mechanical strength 

• Extend across the cytoplasm, giving cells mechanical strength and distributing the mechanical stresses in an epithelial tissue by spanning the cytoplasm from one cell-cell junction to another 

What is the minus end in actin filament

Minus end = slower growing (pointed) end on actin filament 

What is a neurofilament

type of intermediate filament that contribute to axonal diameter which is then important for the speed of action potential  

• Important in axons, especially during development 

• Alteration and accumulation of these in neurons lead to ALS 

What is the plus end in actin filament

Plus end = faster growing (barbed) end on actin filament 

What are some general basics of the cytoskeleton

Cytoskeleton: 

• Spatial & mechanical functions depend on it 

• Made of protein filaments and tubules in an organized structure 

• Important in cell shape, cell movement, internal structure, intracellular transport, intercellular communication, organelle, & cell anchoring 

• Is dynamic and adaptable because of the constant changes the cell undergoes during development, cell cycle, phagocytosis, and other functions 

• Multiple filaments are needed at a time because single filaments are prone to easily breaking but the strong bonds won’t allow them to disassemble quickly 

• Specialized cells use cytoskeletal elements to perform their functions (ex: myofibrils) 

Accessory proteins: help position cells next to each other 

• Motor proteins (dynein, kinesin) with microtubules 

  • “walk” across MT with ATP hydrolysis 

• Tubulins, myosin, actinin, cadherin, vinculin, vimentin, desmin 

What is actin

Actin = microfilaments/thin filaments 

• Protein that links transmembrane proteins to cytosolic proteins 

  • pinches cell shut after division 

  • Whole cell locomotion 

  • Cell surface shape 

• Interacts with microtubules during cell division 

  • Very dynamic/moves around 

• Part of the cortex (@ the periphery and extends to the microvilli)

• Makes up the contractile ring 

What is the actin structure

Structure = 2 types (F or alpha actin) 

• G-actin = each subunit carrying an ATP/ADP (polar) 

• Alpha actin = found in muscle, beta and gamma in all non-muscle cells 

• F-actin = formed from actin subunits assembling head-to-tail (plus to minus end) 

 

• Have structurally different ends  

  • Minus end = slower growing (pointed) 

  • Plus end = faster growing (barbed) *SUBUNITS ADDED TO PLUS END during elongation 

• Complex between actin filaments and the motor protein myosin 

How is actin assembled

Assembly = subunit assembly and disassembly occurs rapidly because of weak non-covalent linkages 

• Filament nucleation is process of initial aggregation 

• Branching nucleation & actin web 

  • Arp2 & Arp3 serve as nucleation hubs 

    • Bind to preexisting actin filaments to form a web and act as a plus end for monomer addition 

• New actin subunits added on the plus end

What are actin filaments

Actin filament = helical polymers of the protein actin 

• Flexible structures that are organized into a variety of linear bundles 

What are myofibrils

Myofibrils (in striated skeletal muscle cytoplasm) consist of sarcomeres 

• Actin & myosin (motor protein) interact here 

• Light band – actin only 

• Dark band – actin and myosin 

 

How does cell movement occur with actin

Cell movement with actin:  

• Protrusion = protruding lamellipodium by polymerizing plus end of actin 

  • Engaged = integrins help move cell forward (protrusion) 

• Attachment and traction = Moves cell in direction if “signal” is worth it 

• Disengaged = retrograde flow backwards 

What are microtubules

Microtubules = made of proteins that position organelles, involved in intracellular transport, and are needed for cell division 

• Long hollow cylinders made of protein tubulin 

• More rigid than actin filaments or intermediate filaments 

• Long & straight and have one end attached to a centrosome 

• Interacts with microtubules during cell division 

  • Binds to chromatid via kinetochore 

• Formed from subunits of tubulin 

• Alpha & beta subunits bind to GTP but ONLY beta uses it (alpha keeps it in the structure) 

• Grow out from centrosome 

  • Microtubule organizing center with embedded centrioles and nucleation sites (important during mitosis) 

How are microtubules formed

Formation = growth occurs at beta end of tubule only 

• Have dynamic instability = sudden conversion from growth to shrinkage and vice verse as long as there is a uniform free subunit concentration 

  • Growth to shrinkage = “catastrophe” 

  • Shrinkage to growth = “rescue” 

• Nucleation occurs in the MTOC (microtubule-organizing center) using gamma tubulin and other proteins that serve as a template that serve as a template for the 13 protofilament structure 

What is MT bending

Bending = linker proteins stop microtubules from sliding and allow them to bend instead 

• Motor action causes bending (bending and NO skiing motion) 

How do motor proteins relate to MT

Motor proteins attach to microtubules & walk using repeated ATP hydrolysis 

• Done by tubulin 

  Motor proteins important  

• Dynein walks toward the negative end of the microtubule 

• Kinesin walks towards the positive end of the microtubule 

 

What are intermediate filaments (descriptive)

Intermediate filaments = several proteins that provide mechanical strength & line the inside of the nuclear envelope 

• Ropelike fibers made of intermediate filament proteins (non-polarized) 

• Form the nuclear lamina 

• Found in vertebrate cells that are required to deal with mechanical stress 

  • Nuclear lamina (inner lining of nuclear envelope), keratins (hair/nails), neurons  

• Do NOT contain a nucleotide binding site (not ATPase) 

• Nonpolar because both ends of the protein are the same 

  • Unclear how it assembles/disassembles - likely through phosphorylation 

• Keratins is the most common type (therefore bind to desmosomes/hemidesmosomes) 

• Make up neurofilaments -> which contribute to rigidity and formation of neurons (contribute to axonal diameter which is important for the speed of the action potential)  

What role does the Sarcoplasmic reticulum play in muscle cells

Holds Ca2+ until it receives signal to release it (used for muscle contraction) 

P-type ATPase calcium pump = best characterized is Ca pump in sarcoplasmic reticulum (SR) of skeletal muscle cells 

• SR serves as intracellular store of Ca in muscle 

• Ca pump moves Ca from the cytosol back into the SR (because need Ca for muscle contraction) 

Calcium pumping cycle = hydrolysis of ATP, phosphate event, antiport 

What is the myosin-actin system

Myosin-actin systems =  

Myosin = motor protein that slides along actin polymers for muscle contraction using ATP hydrolysis 

Muscle contraction = require calcium & troponin 

• Calcium binds troponin, causing tropomyosin to move away from actin so it can bind to myosin to shorten sarcomere and contract muscle 

• Troponin is measured clinically to determine whether an acute heart attack has occurred (stress indicator) 

What is tubulin

Tubulin = The protein subunit of microtubules 

• Alpha & beta subunits bind to GTP but ONLY beta uses it (alpha keeps it in the structure) 

What is a microtubule (simple)

Microtubule = formed from subunits of tubulin 

• Grow out from the centrosome 

What is cilia

Cilia = shorter (than flagella) but beat rhythmically and move fluid over cell surfaces  

• made from microtubules & motor proteins 

• Do NOT move cells 

• Produced by axoneme (core) - image

  • Made of microtubules and associated proteins in a special pattern 

• Found in the respiratory tract, gut epithelium & inner ear hair cells (move sound) 

Primary cilia = serves as a cell signaler or receptor on certain cells (like nasal epithelial cells) 

• Found in call cells (call have a nonmotile cilia = primary cilium) 

• Act as responder to external environment 

What is the flagella

allow cells to swim through liquid media 

• made from microtubules & motor proteins 

• Produced by axoneme (core) - image

  • Made of microtubules and associated proteins in a special patter 

What is troponin

Required for muscle contraction (with calcium)  

• Calcium binds troponin, causing tropomyosin to move away from actin so it can bind to myosin to shorten sarcomere and contract muscle  

• Measured clinically to determine whether an acute heart attack has occurred (stress indicator) 

What is cohesin

involved at the end of S phase to hold sister chromatids together (bracelet) 

• Located at many locations along sister chromatids (keep sister chromatids together) 

• Must be destroyed during metaphase to anaphase transition 

• S-Cdk also stimulates increase in histone protein synthesis for nucleosome synthesis 

How does the cytoskeleton relate to development

ytoskeleton and development:  

• Timing of gene expression for normal protein presence is critical 

• Growth cones = find and form connections with other cells 

  • Tips of growth cones = lamellipodia (filled with actin) 

    • Myosin required to contract the cell 

  • Growth cones grow because of tropic factors (hormones/stimulants/signals) and other substances on/in a substratum 

    • Respond to cues 

  • Growth cones are essential for early development of structures 

• Embryonic development requires extensive cell movement 

  • Actin and tubulin are essential 

  • PIP5Kly plays a role in actin dynamics and focal adhesion formations, therefore, when defective, there are myocardial developmental defects 

How is the cytoskeleton cued to move

Cues to move 

• Growth cones “grow” or “shrink” based on environmental cues 

  • Contact-mediated attraction/repulsion = contact with an adhesion protein in the substrate 

  • Chemoattraction/chemorepulsion = attraction to an emitted chemical cue 

• Some cells “climb” on filaments/tubules formed by other cells to their appropriate positions during development 

What is Kartagener syndrome

hereditary dynein deficits 

• Paralyzed cilia so chronic lung disease due to insufficient movement of cilia from defect in dynein arms 

• Embryonic developmental issues 

• Mutations on 2 genes on chr. 9 

  • Both code for proteins found in the ciliary outer dynein arm lea to this syndrome 

What is epidermolysis bullosa

Blistering diseases caused by alterations in keratins (int. Filament) 

• Genetic defect in keratins  

  • Because keratins bind to hemi/desmosomes (therefore, basal lamina is not held down) 

• Skin ruptures or blisters with any mechanical stress 

What is ALS

ALS = alterations and accumulation in neurofilaments (int. Filaments) in the neuron 

What is spina bifida

Spina bifida = neural tube closure requires numerous cellular events based on cell migration BUT doesn’t happen 

• Caused by vitamin deficiency during pregnancy (aspartic acid?) 

What is Kennedy disease

Kennedy disease = sertoli cells (make sperm) have altered cytoskeleton and lack androgen receptors on nucleus 

• Alterations causes infertility & jaw dropped 

What are myocardial developmental defects

Myocardial developmental defects = associated with impaired intracellular junctions that lead to heart failure and extensive prenatal lethality at embryonic day 11.5 of development 

• Actin disorganized and cadherin missing