Processive acceleration of actin barbed-end assembly by N-WASP.

[wiskott-aldrich syndrome]

Neuronal Wiskott-Aldrich syndrome protein (N-WASP )-activated actin polymerization drives extension of invadopodia and podosomes into the basement layer . In addition to activating Arp 2 /3 , N-WASP binds actin-filament barbed ends , and both N-WASP and barbed ends are tightly clustered in these invasive structures . We use nanofibers coated with N-WASP WWCA domains as model cell surfaces and single -actin-filament imaging to determine how clustered N-WASP affects Arp 2 /3 -independent barbed-end assembly . Individual barbed ends captured by WWCA domains grow at or below their diffusion-limited assembly rate . At high filament densities , however , overlapping filaments form buckles between their nanofiber tethers and myosin attachment points . These buckles grew ∼3 .4 -fold faster than the diffusion-limited rate of unattached barbed ends . N-WASP constructs with and without the native polyproline (PP ) region show similar rate enhancements in the absence of profilin , but profilin slows barbed-end acceleration from constructs containing the PP region . Increasing Mg (2 +) to enhance filament bundling increases the frequency of filament buckle formation , consistent with a requirement of accelerated assembly on barbed-end bundling . We propose that this novel N-WASP assembly activity provides an Arp 2 /3 -independent force that drives nascent filament bundles into the basement layer during cell invasion .

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adrenal incidentaloma

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cushing syndrome

dedifferentiated liposarcoma

dracunculiasis

dystrophic epidermolysis bullosa

esophageal carcinoma

focal myositis

heparin-induced thrombocytopenia

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hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

omenn syndrome

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

sneddon syndrome

thoracic outlet syndrome

von hippel-lindau disease

wiskott-aldrich syndrome

x-linked adrenoleukodystrophy

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