Eps8 regulates axonal filopodia in hippocampal neurons in response to BDNF

The regulation of filopodia plays a crucial role during neuronal development and synaptogenesis. Axonal filopodia, which are known to originate presynaptic specializations, are regulated in response to neurotrophic factors. The structural components of filopodia are actin filaments, whose dynamics and organization are controlled by ensembles of actin binding proteins. How neurotrophic factors regulate these latter proteins remains, however, poorly defined. Here, using a combination of mouse genetic, biochemical and cell biological assays, we show that genetic removal of Eps8, an actin-binding and regulatory protein enriched in the growth cones and developing processes of neurons, significantly augments the number and density of VASP-dependent axonal filopodia. The reintroduction of Eps8 WT, but not an Eps8 capping-defective mutant into primary hippocampal neurons restored axonal filopdia to wild type levels. We further show that the actin barbed end capping activity of Eps8 is inhibited by BDNF treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation

Observation of B meson decays to b(1)pi and b(1)K

We present the results of searches for decays of B mesons to final states with a b(1) meson and a charged pion or kaon. The data, collected with the BABAR detector at the Stanford Linear Accelerator Center, represent 382x10(6) B(B)over bar pairs produced in e(+)e(-) annihilation. The results for the branching fractions are, in units of 10(-6), B(B+ -> b(1)(0)pi(+)) = 6.7 +/- 1.7 +/- 1.0, B(B+ -> b(1)(0)K(+)) = 9.1 +/- 1.7 +/- 1.0, B(B-0 -> b(1)(-/+)pi +/- ) = 10.9 +/- 1.2 +/- 0.9, and B(B-0 -> b(1)(-)K(+)) = 7.4 +/- 1.0 +/- 1.0, with the assumption that B(b(1) -> omega pi) = 1. We also measure charge and flavor asymmetries A(ch)(B+ -> b(1)(0)pi(+)) = 0.05 +/- 0.16 +/- 0.02, A(ch)(B+ -> b(1)(0)K(+)) = -0.46 +/- 0.20 +/- 0.02, A(ch)(B-0 -> b(1)(-/+)pi +/- ) = -0.05 +/- 0.10 +/- 0.02, C(B-0 -> b(1)(-/+)pi +/- ) = -0.22 +/- 0.23 +/- 0.05, Delta C(B-0 -> b(1)(-/+)pi +/- ) = -1.04 +/- 0.23 +/- 0.08, and A(ch)(B-0 -> b(1)(-)K(+)) = -0.07 +/- 0.12 +/- 0.02. The first error quoted is statistical, and the second systematic

Amplitude analysis of the decay D0→K-K+π0

Using 385 fb(-1) of e(+)e(-) collisions, we study the amplitudes of the singly Cabibbo-suppressed decay D-0 -> K-K+pi(0). We measure the strong phase difference between the (D) over bar (0) and D-0 decays to K-*(892)K-+(-) to be -35.5 degrees +/- 1.9 degrees(stat)+/- 2.2 degrees(syst), and their amplitude ratio to be 0.599 +/- 0.013(stat)+/- 0.011(syst). We observe contributions from the K pi and K-K+ scalar and vector amplitudes, and analyze their angular moments. We find no evidence for charged kappa, nor for higher spin states. We also perform a partial-wave analysis of the K-K+ system in a limited mass range