Molecular Fundamentals - Cytoskeleton and Intracellular Traffic

what does the following describe?

• is the framework of linear structures

• gives the cell its shape (“skeleton of the cell”)

• holds organelles in place

• coordinates molecular traffic inside the cell

• allows for movement and changes in the shape of the cell

cytoskeleton

intermediate filaments, microtubles, and actin filaments are the three major components of what?

the cytoskeleton

what component’s structure appears like several strands twisted together to provide tensile strength (ropelike structure)?

intermediate filaments

intermediate filaments enables cells to do what?

withstand mechanical stresses

what are the four classes of intermediate filaments?

• keratins (in epithelia)

• vimentin and vimentin-related (in connective tissue, muscle cells, and glial cells)

• neurofilaments (in nerve cells)

• nuclear lamins (in all animal cells)

intermediate filaments are prominent in cells that need to withstand various mechanical stresses such as?

• skin cells

• long axons of nerve cells

• muscle cells

in epithelium, intermediate filaments join cells together through what?

adherent junctions: desmosomes and hemidesmosomes

intermediate filaments form a two dimensional mesh structure that strengthens the nuclear membrane called what?

nuclear lamina

what is the considered the “highway” of the cell?

microtubles

microtubules are present in what?

all nucleated cells and the platelets in the blood

microtubules are _______ structures.

polar structures:

• plus end (β-tubulin end)

• minus end (α-tubulin end)

microtubules exhibit what?

“dynamic instability”

the “dynamic instability” of microtubules causes them to do what?

rapidly grow and shrink due to the GTP hydrolysis activity of the α/β-tublin dimer

what is a centrosome considered?

microtubule organizing center (MTOC)

where are the plus and minus ends of microtubules in regards to the centrosome found?

• plus ends are oriented away from the centrosome

• minus ends are at the centrosome

cytoskeleton acts as a _________ system inside the cell

transportation

what is the function of molecular motors?

transport organelles and membrane-bound vesicles to their target locations within the cell

the movement of molecular motors is _________ and requires _________?

• unidirectional

• energy (ATP dependent)

what are two types of microtubule-associated molecular motors?

kinesin and dynein

what direction does kinesin move?

toward the plus end of microtubule

what direction does dynein move?

toward minus end of microtubule

dyneins move materials from what and to where?

from the axon terminal to the cell body along microtubules

some materials that are synthesized in the cell body of a neuron must be transported by what and to where?

by kinesins to the axon terminal along microtubules, toward plus end

what describes cilia?

hair-like structures covered by plasma membrane that extend from the cell surface (found in respiratory tract, fallopian tubes)

what describes flagella?

structurally similar to cilia but only one per cell; in humans, only found in on sperm cells

actin is present in what cells?

all cells

what are thin, flexible, linear structures composed of actin subunits?

actin filaments

what is a key component in cellular movement?

actin filaments

like microtubules, actin filaments have _________.

polarity

what is the purpose of microvilli?

increase the surface area of the cell to help with absorption; found on epithelial cells in the small intestine

the following are all examples of what?

• contractile bundles in cytoplasm

• sheet-like and finger-like protrusions on the leading edge of motile cells

• contractile ring during cell division

actin filaments

what are the two types of cilia?

motile and non-motile

cilia are composed of what?

microtubules

some cilia are used to do what?

move the cell or to move objects over the surface of the cell

microvilli are _______ motile.

never

microvilli are composed of what?

actin filaments

what do microvilli enhance and increase?

• enhance the surface area of the cell

• increase the rate of diffusion of materials into the cell

actin filaments are also what kind of structures?

dynamic structures

what describes how actin filaments can grow and shrink?

can grow from one end (plus end) while simultaneously disassembling from the opposite end (minus end)

what end do actin filaments grow from?

plus end

what end do actin filaments shrink from?

minus end

what end do microtubules grow from?

plus end

what end do microtubules shrink from?

plus end

what is the nucleoside triphosphate in microtubules?

GTP

what is the nucleoside triphosphate in actin filaments?

ATP

actin filaments can also be associated with what?

specific molecular motors (myosin family)

most myosin heads walk along the actin filament toward what end?

toward plus end

actin and myosin play important roles in what?

muscle contraction

myosin heads walking along actin filaments produces what?

shortening of the sarcomere (muscle contraction)

what two regulatory proteins prevent myosin thick filaments from moving along the actin thin filaments in the absence of a signal for contraction?

tropomyosin and troponin

what describes tropomyosin?

lay end to end along the actin filament, concealing the myosin-binding sites

what describes troponin?

Ca²⁺ sensitive protein that uncovers the Myosin-binding site when intracellular Ca²⁺ concentrations rise

what describes exocytosis?

• transport vesicle fuses with the plasma membrane and its contents are released into the extracellular space

• vesicle membrane becomes continuous with the plasma membrane

what describes endocytosis?

• a plasma membrane patch is internalized, forming a transport vesicle

• the contents of this vesicle are derived from the extracellular space

__________ ____________ bud off from one compartment and fuse with another

transport vesicles

__________ requires membrane fusion initiated from the lumenal side of the membrane

budding

_____________ ___________ requires a membrane fusion event initiated from the cytoplasmic side of both the donor and target membranes

vesicle fusion

what are the three major types of coated vesicles?

• clathrin-coated

• COPI-coated

• COPII-coated

what describes clathrin-coated vesicles?

transport from plasma membrane to golgi apparatus, from golgi to late endosomes, and from secretory vesicles to golgi

what describes COPI-coated vesicles?

retrograde transport from golgi to ER

what describes COPII-coated vesicles?

transport from ER to cis golgi

what is the Sar1?

coat-recruitment GTPase responsible for COPII coat assembly at the ER membrane

what becomes concentrated in transport vesicles as they leave the ER?

cargo receptors and associated cargo

what binds to the cargo receptors?

soluble cargo proteins

vesicles that are transitioning from the ER to the cis Golgi fuse together to form what?

vesicular tubular clusters

fusion of vesicular tubular clusters is mediated through what?

the interactions of surface-bound molecules called SNARES

the vesicular tubular clusters move along microtubules toward what?

cis Golgi

what directions do vesicles use kinesins and microtubules to move?

from ER toward Golgi and from Golgi toward plasma membrane

what directions do vesicles use dyneins and microtubules to move?

from plasma membrane toward Golgi and from Golgi toward ER

what directions do vesicles use myosin and actin filaments to move?

toward plus end of actin filaments

after fusion of the vesicular tubular cluster with the cis Golgi, the ER cargo receptors have to be what?

recycled back to the membrane

soluble ER resident proteins should remain where?

in ER

soluble ER resident proteins contain what?

a specific amino acid sequence: Lysine-Aspartate-Glutamate-Leucine (KDEL)

what do KDEL receptors do?

pick up soluble ER resident proteins in the golgi and package them into COPI coated vesicles

how do KDEL receptors bring back soluble resident proteins to the ER?

through COPI coated vesicles

clathrin-coated vesicles transport material from what?

from the plasma membrane and between endosomal and Golgi compartments

clathrin coats are made up of subunits called what?

triskelions

clathrin interacts with what?

adaptor proteins on the surface of membranes

clathrin coated vesicles that bud from different membranes use different adaptor proteins and therefore do what?

package different cargo molecules

as clathrin-coated bud grows, what forms?

dynamin forms a ring around the neck of the bud

dynamin uses energy from what?

GTP hydrolysis

each organelle in the secretory and endocytic pathways express what?

specific types of Rab proteins

when the vesicle buds off, the Rab protein that is displayed on its cytoplasmic surface does what?

specifies the target location of the vesicle

target membranes display proteins on their surface called what?

Rab effectors

Rab effectors bring the vesicle close enough to the target membrane for what?

to allow for v-SNARE and t-SNARE interactions that will mediate fusion of the two membranes

what do SNAREs do?

catalyze the membrane fusion reactions in vesicular transport

where are v-SNAREs found?

on vesicle membranes

where are t-SNAREs found?

on target membranes

the helical domains of the v-SNAREs and t-SNAREs wrap around each other to form what?

trans-SNARE complex that holds the vesicle membrane close to the target membrane

endocytic vesicles originating from the plasma membrane bud off using what to do what?

clathrin coats and fuse with early endosomes

early endosomes make _________ _________ and fuse with _________ __________.

• multivesicular bodies

• late endosomes

where are early endosomes found?

just inside the plasma membrane and have a pH of 6

where are late endosomes found?

closer to the Golgi and nucleus and have a pH closer to 5

late endosomes fuse with lysosomes, forming what?

endolysosomes

what are lysosomes filled with?

acid hydrolases

how is the acidic environment of lysosomes maintained?

through the activity of V-type ATPases that pump protons into the organelle

how are lysosomal enzymes are modified in the golgi?

by the addition of mannose-6 phosphate (M6P)

where are receptors for M6P found?

on the membrane of the trans Golgi network

once the lysosomal enzyme is in the endosome what happens and why?

the phosphate is removed from the enzyme so that the enzyme is not brought back to the Golgi when M6P receptors are recycled

what are the three pathways to degradation in lysosomes?

• phagocytosis

• endocytosis

• autophagy