Exam 1 9/8 Kingsley Flashcards
3 major components of the cytoskeleton
- microfilaments
- intermediate filaments
- microtubules
Synonymous names for microfilaments
thin filaments, actin filaments
Describe the structure of microfilaments (actin filaments)
G-actin monomers polymerize –> coil to form F-actin (filamentous form)
2 chains of globular protein, 6-8 nm thick
G-actin makes up how much of cellular actin content?
Half
Critical concentration of free actin is 0.2 micromoles, is lower than actual intracellular concentration. It should all polymerize, but why doesn’t it?
G-actin is bound by profilin and beta thymosin. Prevents polymerization until needed
Actin polymerization requires:
ATP
What is hydrolyzed during actin polymerization?
ATP; ADP becomes trapped in polymer
What monovalent cation is required during actin polymerization?
K+
What divalent cation is required during actin polymerization?
Mg2+
What terminates f-actin elongation?
capping proteins that attach to + end. gelsolin, cofilin, and severin are the capping proteins listed
What regulates f-actin capping proteins?
ADP, ATP, Ca2+
What removes f-actin capping proteins?
Polyphosphoinositide. This facilitates f-actin lengthening
Examples of actin-binding proteins
myosin, gelsolin, fimbrin, spectrin, talin, alpha-actinin
What are 3 main functions of actin-binding proteins?
capping, forming actin bundles, motility/adhesion
Actin filaments form:
bundles
Actin filaments vary in ____, which is determined by _____
length; function (non-muscle)
What are 3 main types of actin bundling?
- contractile bundling
- gel-like networks
- parallel bundles
What are some functions of contractile bundles?
- movement of organelles and vesicles
- endocytosis/exocytosis
- filapodia
- mitotic division (contractile rings)
contractile bundles are associated with:
myosin
How are contractile bundles arranged?
- loosely arranged and branched
- parallel to each other
- alternating + and - ends (myosin binding helps determine polarity)
Myosin I function
formation and retraction of cell protrusions
Myosin II function
forms thick filaments (15 nm), moves actin filaments (muscle)
Myosin V
participates in vesicle movement along actin
Describe gel-like bundles
membrane and cytoplasmic actin-rich network, maintains cell shape and structure, linked with other proteins
Parallel bundles have closely packed F-actin associated with:
fimbrin and villin proteins, which assemble f-actin to form microvilli
Villin
actin binding protein that stays pushed out due to gel like bundle. increases surface area in the intestines
Focal adhesion two main components
P-face ABP form attachments to cytoskeleton
E-face integrins link to ECM
Integrins are:
transmembrane glycoproteins
Integrins bind:
ECM to cytoskeleton; alpha/beta subunits bind ECM; beta subunits bind ABP; bind f-actin
What are filopodia?
actin rich membrane protrusions. Made of contractile bundles
Lamellipodia
leading edge of migrating cell, made of gel-like bundles
Filapodia and lamellipodia are anchored by:
focal adhesions; integrin mediated
Phalloidins
toxins from amanita mushroom
What do phalloidins do, and what is the remedy?
binds actin filament and prevents depolymerization (disturbs membrane flow and liver cell function). Remedy is eat raw meat to allow actin/myosin to bind phalloidin and reduce the toxicity
Size of intermediate filaments
8 to 10 nm
Desmosomes are a type of what kind of filament?
intermediate filament
Desmosomes function
anchor cell-cell junctions
Hemidesmosomes are a type of what kind of filament?
intermediate filaments
Hemidesmosomes function
anchor cell-matrix junctions
Desmosomes and hemidesmosomes together maintain:
cell shape and polarity
Structure and assembly of intermediate filaments
- monomers form coiled dimers
- anti-parallel dimers form tetramers
- Tetramer is non-polar unit of IF
- tetramers form protofilaments –> form protofibrils –> thus forms IF
Tetramer subunit varies upon type of:
IF
Types of IF
keratins, desmin, vimentin, neurofilaments, flial fibrillary acidic protein, nuclear lamins
Why is DNA methylation mitotically heritable?
to maintain tissue differentiation
DNMT I
DNA methyltransferase; maintains tissue differentiation during replication; active in normal, differentiated tissues
DNMT I recognizes:
hemi-methylated DNA –> keeps cellular identity
____ is highly activated in aggressive tumors
DNMT 3 (moves DNA methyl marks, turns of methylation genes, methylated cpg island)
What does DNMT3 cause?
may expose (turn on) other genes, dysplasia
What is a tumor marker in carcinomas
Cytokeratin (type of IF)
Zona occludens another name
tight junctions
Primary intercellular diffusion barrier
zona occludens
Zona occludens allows for what between tissues?
physiochemical separation
Where is zona occludens found?
apical surface between adjoining epithelial cells (ex: mucosal epithelial cells, skin cells)
major proteins associated with zona occludens:
claudins, occludins –> function as seal/zipper between cells
How to tight junctions interact?
Via ZO-1 (zona occludens-1) with actin in the cytoskeleton
What is zonula adherens?
network of additional cell-cell junctions
Zonula adherens is mediated via transmembrane glycoprotein _____, which is located on the E face
cadherins
How do cadherins form cell-cell junctions/bind cytoskeleton?
- link to catenin, vinculin found on actin filaments
- alpha-actinin links adjacent actin filaments together
Cadherins are responsible for _____ and ____ cell-cell adhesion and are _____ dependent
homotypic; heterotypic; Ca2+ dependent
What do cadherins link to, and where?
actin filaments on neighboring cells
Another name for desmosomes
macula adherens
Function of desmosomes
Strong cell-cell adhesion, links intermediate filaments, provide mechanical structure
What proteins make up desmosomes
Desmoglein, desmocollin (E face)
Desmoplakins, plakoglobins (P face)
Desmoglein and desmocollin are ___ dependent
Ca2+
Hemidesmosomes
cell-to-ecm junctions
How do hemi-desmosomes bind cell to ECM?
- integrin heterodimers bind ECM extracellularly
- integrins anchored to cytoplasmic proteins, which connect to intermediate filaments
Regarding hemidesmosomes, which proteins stabilize integrin-cytoskeleton attachment?
BPAG, erbin
Focal adhesions function
mediates adhesion and migration
Focal adhesions link with:
stress fibers
What are two main components of focal adhesion?
- P-face ACP form attachments to cytoskeleton
- E-face integrins link to ECM
How do focal adhesions bind to ECM?
Through integrins
- a, b subunits of integrins bind ECM
- b subunits binds ABP
- a-actinin, vinculin
- bind F- actin
Contractile bundles function
movement of vesicles, organelles, cell adhesion and migration
Filopodia
actin rich membrane protrusions; feet of moving cells
Filopodia have
contractile bundles
Lamellipodia
leading edge of migrating cell; sheet of actin mesh
Lamellipodia have
gel-like bundles
Filopodia and lamellipodia are anchored by:
focal adhesions
What are microtubules/their function?
- largest cytoskeletal elements
- structural component of centrioles
- structural component of cilia, flagella
- intracellular vesicle transport
Microtubule structure
13 circular arrays of dimerized tubulin (parallel protofilaments) - alpha/beta tubulin dimer with GTP
Microtubule polarity is established by:
gamma tubulin (MTOC)
Microtubules require both ___ and ____
GTP and Mg2+
Microtubules exhibit:
dynamic instability
How is dynamic instability regulated?
MAPs (microtubule associated proteins)
- one listed in red is tau
Where are MAPs found? (microtubule associated proteins)
regular intervals along polypeptide
Two primary functions of MAPs
polymerization/depolymerization assist in organelle/vesicle movement
MAPs move ____ using ___ and ____
cargo; dynein(-) and kinesin (+)
What direction does kinesin travel?
- to + (anterograde)
What direction does dynein travel?
+ to - (retrograde)
______ are a primary site of MT nucleation
Centrosomes
Centrioles structure
Nine triplets of microtubules
What is the kinetochore?
complex of proteins where microtubules attach during cell division
Where is kinetochore located?
centromere of chromosome
Microtubules form ____ in cilia and flagella
doublets
Microtubules form ____ in basal bodies and centrioles
triplets
Flagella are powered by:
ATP
Cilia are powered by:
ATP
Where are cilia found?
mucociliary escalator (immune system); fallopian tubes