Lecture 14 - Kinesins

Intracellular motility

Shinya Inoue

thryone sperm acrosomal extension

Robert Allen

AVED-DIC

MT based motility

Scott Brady

worked with Allen + Ray Lasek

used AVEC-DIC on axoplasm

documented movement of material

Ron Vale

discovered kinesin from axoplasm

kinesins

use ATP hydrolysis to move towards + end of MT

anterograde movement

kinesin-1

moves processively

moves cargo

kinesin-1 head

2 heads

10nm

binds MT

catalyzes ATP hydrolysis

kinesin-1 tail

coiled coil

binds cargo

light chains

myosin vs kinesin

similar

myosin has bigger heads

myosin binds actin

kinesin movement

8 steps @ 0.8um/s

one head binds, one head releases (they walk)

fold up (head→tail) when inactive

kinesin families

14+

general structure of head, coiled coil, tail

kinesin-3

Kif1

single headed = must dimerize

fast and processive

Kif1 a → mitochondria

Kif1 B → synaptic vesicles precursor

kinesin-7

CENP-E

large

processive steps (fast-vitro, slow-vivo)

moves chromosomes during metaphase

kin-7 phosphorylation

aurora kinases - add P

PP1 - removed P

kinesin-13

Kif2a, Kif2b, Kif2c, Kif24

internal motor domains

ATP depolymerizes MT

shortens kinetichores during anaphase

kinesin-14

\- end directed

motor domain at c-terminus

neck puts head at wrong position

processive when 2+ bind to one cargo

20-50nm slow steps

kinesin-dynein

bind transmembrane proteins

allow for movement in both directions

acetylation of a-tubulin

increased kin-1 affinity

detyrosination of a-tubulin

increased kin-1 affinity

polyglutamination of c-terminal tails of a and B tubulin

decreased kin-3

KIF1B loss of function

charcot marie tooth type 2A

KIF5A mutation

hereditary spastic paraplegia

KIF5C mutation

amyloid precursor protein = alzheimers

KIF3/kin-3 mutation

kidney = polycystic kidney disease

eye = retinisis pigmentosa