Funktion von Abp1, einem Signal-responsiven Verbindungsglied zwischen Aktinzytoskelett und Membrantransport, in neuronaler Morphologie = Function of Abp1, a signal-responsive linker between actin cytoskeleton and membrane transport, in neuronal morphology

Häckel, Akvile

Polymerization and organization of actin into complex superstructures is indispensable for structure and function of neuronal networks. This work shows that the F-actin-binding protein 1 (Abp1), which controls Arp2/3 complex-mediated actin nucleation via the neural Wiskott-Aldrich syndrome protein (N-WASP) and binds to postsynaptic scaffold proteins of the ProSAP/Shank family, has a profound impact on synaptic organization. RNAi mediated knock-down of Abp1 expression results in changes in early axon development virtually identical to Arp2/3 complex inhibition, i.e. a selective increase of axon length. This work reveals an essential role of Abp1 and its cooperation with Cdc42 in N-WASP-induced rearrangements of the neuronal cytoskeleton. Secondly, Abp1 controls the formation and morphology of dendritic spines harboring the postsynaptic signal reception and transduction apparatus. Overexpression of the two Abp1 F-actin-binding domains increases the length of spines but dramatically reduces mushroom-type spine density, due to lack of the Abp1 SH3 domain. In contrast, overexpression of full-length Abp1 increases mushroom spine and synapse density. This suggests that both actin-binding and SH3 domain interactions are crucial for Abp1’s role in spine maturation. Abp1 hereby works in close conjunction with ProSAP1/Shank2 and ProSAP2/Shank3, because ProSAP2 RNAi suppressed Abp1 effects, and the ProSAP/Shank-induced increase of spine head width is further promoted by Abp1 cooverexpression and reduced upon Abp1 knock-down. Spine head extension furthermore depends on local Arp2/3 complex-mediated actin polymerization, which is controlled by Abp1 via the Arp2/3 complex activator N-WASP. Abp1 thus plays an important role in the formation and morphology control of synapses by making a required functional connection between PSD components and postsynaptic actin dynamics. It furthermore is crucial for cytoskeletal processes underlying proper early neuronal network formation.

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Häckel, Akvile: Funktion von Abp1, einem Signal-responsiven Verbindungsglied zwischen Aktinzytoskelett und Membrantransport, in neuronaler Morphologie = Function of Abp1, a signal-responsive linker between actin cytoskeleton and membrane transport, in neuronal morphology. 2010.

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