Cytoskeleton II Flashcards
Cyto skeleton motor dependent types
Motor driven or polymerization-driven
Intracellular transport-motor-driven or polymerization-driven
Ciliar/flagellar beating
What makes up contractile ring/what is its function
Actin and myosin filaments
Used to cleave the cell in two
How does city skeleton drive morphogenesis
Invagination of epithelial sheet is caused by organized tightening of adhesion belts
-associated with actin filaments/myosin II
Traffic direction
Both ways on actin and MT
3 classes of cytoskeletal motors
Myosins-move along actin filaments
Dyneins/kinesins-move along Mts
(dynein is much bigger)
All three classes are ATP ases and have multiple isomforms encoded by multiple ones
Molecular motor facts (5)
All atpases
Related structure and mechs-large gene families
Partiulular isoform moves in one direction
Vesiceles/organelles move on microtubules and actin filaments + more than one kind of motor
Downstream targets of cellular signalling cascades
Molecular motor energetics
Energy from ATP hydrolysis-causes conformational change
-tension or moments is generated along filament or MT
Myosin facts
Large gene family
Two heavy chains, tw or more light chains
Most move toward plus direction
Globular head with Atlases
Tail is variable domain-coiled coil for dimerization and/or binds to membrane or target vesicle
Classification based on motor domain
Mutations-result in inherited human diseases
Kinesin facts
Motor domain (head)-heavy chains contain ATPase and MT binding site
- N terminal is plus end directed
- C terminal is minus end directed
Kinesin 1C is bound to tail
Neckregion determines opolarity
Stalk is coiled for dimerization
Tail binds to varaible target and to light chains
Dyenin facts
Minus end directed
Big
AAA proteins (ATPase associated with diverse cellular activities) -energy from hydrolysis, conformationatal change, work
In cilia/flagella
From periphery of cell to nucleus
Can see in EM as little spur
When has ATP bounds attached to microtubule
-lose P and released
Karatagener syndrome
Primary ciliary dyskinesia
Resp tract infections/male infertility
Mislocalized dyenin-stuck in basal body
Cilia are immotile-mutation is in outer arm ciliary dyne heavy chain, outer arms mmissing
How do cytoskeletal motors work
ATP energy to mechanical work and heat
-conformational change
rate limiting step is Phosphate release following hydrolysis
- binding to actin or microtubules accelerates rate limiting step
- actin/MT is nucleotide exchange factor
Kinesin and myosin differ in processivity
Myosin II firing
Add ATP- conformational change and release, before hydrolysis
- add ATP-release from actin
- recovery stroke occurs
Release ATp-rebind-actin speeds up, power stroke-rigor mortis–stuck on-actin
What determines myosin speed
rate of myosin ATPase
How reg function of myosin
OM (drug)-binds to cardiac myosin, increases contractility bu accelerating Phospaht erelease-accelerating transition to strong bind and icnreaesd force
Kinesin firing
Bind of ATP weakens affinity for MT
P lease-binds with higher affinity
MT binding accelerates product release and conversion from weak to strong binding (power stroke)
Power stroke
Conversion of weak to strong binding
Kinesan walking
Trai]ling head has ADP and weakly associates wit hMT
ATP head bond to MT
They switch when ATP is hydrolyzed and adde
Motor, substrate track and direction of movement
Myo-ATP-actin-Plus end (mostly)
Kinesan-ATP-MT-Plus end (mostly)
Dyenin-ATP-MT-Minus end
Localization of motors
Tail determins localization
-bind to specific targets
head determines classifcatio/identity/motor function
Antibodies also allow localization of myosin and kinesin isoforms
What is between motor and cargo
Sometimes many proteins that allow great increase of specificity and regulation
-scaffoleer, adaptor, direct bind etc.
Dynactin
Multifunctional protein complex that increases precocity of dyenin-helps bind to MT and other proteins
Binds to tail of dyeing
Has many parters including spectrin that help binding
Which way does traffic go on MT’s and actin
Both ways-can be short or long
Intracellular transport facts
many things are transported from ER to cell periphery and back
Transport can occur on _ end of MT as MT grows
Vesicles/organleles can have more than one molecular motor=can travel on both MT and actin
Transport of pigment granulaes
Pigment is in melanosome vesiceles
(melanocytes-cells that make pigment)
Redistribution requires transport on MT and actin filaments
Melanocytes are from neural crest cells
Myosin 5-if don’t have won’t have normal pigmentation
Myosin V
Binds to carbgo via melanophilin and RabGTPs
Need entire thing to move melaosomes
Myosin 5 attaches from actin to the melanosome
Ras GTPases
target myosin to specific intracellular membranes
if defeiceint-cant target to specific area-cluster in areas where they shouldn’t be
Griscelli type 1
elejalde syndrome
Silvery hair, light skin in child of dark skinned parents
neuro defects
Bigpment clumped in hair and not distributed as in normal hair
Malosomes stunch in basal ep-not anywhere else
