Microfilament Motors

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Skeletal (Striated) Muscle Sliding filament contraction

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Z

ZM

animation

Myosin II StructureAFM

Control by Troponin/Tropomyosin

Ca++

The Swinging Lever Arm

+ ATP ->ADP+Pi - Pi, ADP

Minus Plus

Muscle Myosin (II)

Plus Minus

animation

Making its moves

Minus

Plus

animation

GFP-Myosin in a

Cardiomyocyte

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video

Stress-Mediated Orientation

The Myosin Family Tree (24 and growing)

Myosin Alignments

From the Fold (the Ur-Motor?)

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Myosin Classes

Myosin class

Animals Fungi Dictyo-stelium

Plants Apicomplexans

Kineto-plastids

I X X X X

II X X X

III X

IV *

V X X ?

VI X ? X

VII X ?

VIII X

IX X

X *

XI X

XII *

XIII *

XIV X

XV X

XVI *

XVII *

XVIII X

XIX *

XX *

XXI X

XXII X

XXIII X

XIV X

X = present* = limited

Saccharomyces cerevisiae

Gene Myosin class

Involved in function

Mutant phenotype

MYO1 class II cell division myo1=forms cell chains

MYO2 class V polarized growth

myo2 = can't bud

MYO3 class I endocytosis myo3,5 double mutant defective in endocytosis

MYO4 class V cell fate myo4 = mother/daughter mating type switching defective

MYO5 class I endocytosis myo3,5 double mutant defective in endocytosis

Myosins Everywhere!QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.

39 myosins in the human genome, and counting!

In Vitro Motor Assays

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Myo IXb is a plus-end directed motor

(because the polarity marked microfilament,

red at the plus end, moved in a minus-end

direction over the motor)

Myo II

video

video

MyoMotors, Inc.

Differential localization

Myosin I

Myosin II

Myo V Stepping

out

A flip-book animation

Plus

Rab27Melanophilin

Melanosome

37nm 37 nm per step 74 nm per stride

Running in reverse

Barbed-end myosins move in plus-end directions

Pointed-end myosins move in minus-end directions

Myosin VI has an insertion in the converter region that changes its lever arm

Myo VI

and

Myo V

Can you hear me now?

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Myosin Mutations

Create Deafness

Normal stereociliary bundles in the cochlea

are disorganized in a Myosin VIIa waltzer mutant

5 um

Myosin VI localization

Myosin XVa-GFP

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microfilaments

video

MyoX-GFP

Phosphoinositide lipid binding

domains