Rho‐associated coiled‐coil kinase 1 activation mediates amyloid precursor protein site‐specific Ser655 phosphorylation and triggers amyloid pathology

Rho‐associated coiled‐coil kinase 1 (ROCK1) is proposed to be implicated in Aβ suppression; however, the role for ROCK1 in amyloidogenic metabolism of amyloid precursor protein (APP) to produce Aβ was unknown. In the present study, we showed that ROCK1 kinase activity and its APP binding were enhanced in AD brain, resulting in increased β‐secretase cleavage of APP. Furthermore, we firstly confirmed that APP served as a substrate for ROCK1 and its major phosphorylation site was located at Ser655. The increased level of APP Ser655 phosphorylation was observed in the brain of APP/PS1 mice and AD patients compared to controls. Moreover, blockade of APP Ser655 phosphorylation, or inhibition of ROCK1 activity with either shRNA knockdown or Y‐27632, ameliorated amyloid pathology and improved learning and memory in APP/PS1 mice. These findings suggest that activated ROCK1 targets APP Ser655 phosphorylation, which promotes amyloid processing and pathology. Inhibition of ROCK1 could be a potential therapeutic approach for AD.     

Distinct RopGEFs Successively Drive Polarization and Outgrowth of Root Hairs

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Structural Basis for the Dual Substrate Specificity of DOCK7 Guanine Nucleotide Exchange Factor

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Spatially Distinct Pools of TORC1 Balance Protein Homeostasis

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Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3

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How pollen tubes grow

Sexual reproduction of flowering plants depends on delivery of the sperm to the egg, which occurs through a long, polarized projection of a pollen cell, called the pollen tube. The pollen tube grows exclusively at its tip, and this growth is distinguished by very fast rates and reaches extended lengths. Thus, one of the most fascinating aspects of pollen biology is the question of how enough cell wall material is produced to accommodate such rapid extension of pollen tube, and how the cell wall deposition and structure are regulated to allow for rapid changes in the direction of growth. This review discusses recent advances in our understanding of the mechanism of pollen tube growth, focusing on such basic cellular processes as control of cell shape and growth by a network of cell wall-modifying enzymes, molecular motor-mediated vesicular transport, and intracellular signaling by localized gradients of second messengers.     

Biochemical characterization of distinct regions of SPEC molecules and their role in phagocytosis

Cdc42 signaling pathways play important roles in immune cell polarization and cytoskeletal changes. Although the small Cdc42-binding proteins SPEC1 and SPEC2 play a role in F-actin accumulation in activated T lymphocytes, little is known about their precise activities in other cell types. Here, we mapped the Cdc42-binding activity of SPEC1 to the CRIB sequence and a downstream alpha helical region. Biochemical studies revealed that SPEC1 did not interact with a Rac1 switch-of-function mutant capable of inducing Cdc42-like filopodia, potentially eliminating a role for SPECs in this process. A phosphoinositide-binding region was identified within a basic region N-terminal to the CRIB sequence of SPEC1. Using an anti-SPEC2 antibody, we found that endogenous SPEC2 colocalized with Cdc42 at the phagocytic cup of macrophages internalizing zymosan A particles prior to significant F-actin accumulation. Overexpression studies of the related SPEC1 protein induced marked macrophage contraction and prevented particle binding and phagocytosis. Although a Cdc42-binding mutant of SPEC1 still caused macrophage contraction, mutations within the N-terminal cysteines and phosphoinositide-binding region reversed macrophage contraction but still resulted in impaired phagocytosis. These results identify three distinct structural and functional regions within SPECs and demonstrate their likely role in early contractile events in phagocytosis.