Excitation-contraction coupling inhibitors potentiate the actions of botulinum neurotoxin type A at the neuromuscular junction.

Background And Purpose: Botulinum neurotoxin type A1 (BoNT/A) is one of the most potent neurotoxins known. At the same time, it is also one of the safest therapeutic agents used for the treatment of several human disorders and in aesthetic medicine. Notwithstanding great effectiveness, strategies to accelerate the onset and prolong BoNT/A action would significantly ameliorate its pharmacological effects with beneficial outcomes for clinical use.

A New TGF-β Mimetic, XEP™-716 Miniprotein™, Exhibiting Regenerative Properties Objectivized by Instrumental Evaluation.

Introduction: Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations.

Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN.

Oriented cell divisions are necessary for the development of epithelial structures. Mitotic spindle orientation requires the precise localization of force generators at the cell cortex via the evolutionarily conserved LGN complex. However, polarity cues acting upstream of this complex in vivo in the vertebrate epithelia remain unknown.

SLK-dependent activation of ERMs controls LGN-NuMA localization and spindle orientation.

Mitotic spindle orientation relies on a complex dialog between the spindle microtubules and the cell cortex, in which F-actin has been recently implicated. Here, we report that the membrane-actin linkers ezrin/radixin/moesin (ERMs) are strongly and directly activated by the Ste20-like kinase at mitotic entry in mammalian cells. Using microfabricated adhesive substrates to control the axis of cell division, we found that the activation of ERMs plays a key role in guiding the orientation of the mitotic spindle.

An ARF6/Rab35 GTPase cascade for endocytic recycling and successful cytokinesis.

Cytokinesis bridge instability leads to binucleated cells that can promote tumorigenesis in vivo. Membrane trafficking is crucial for animal cell cytokinesis, and several endocytic pathways regulated by distinct GTPases (Rab11, Rab21, Rab35, ARF6, RalA/B) contribute to the postfurrowing steps of cytokinesis. However, little is known about how these pathways are coordinated for successful cytokinesis.

Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis.

Abscission is the least understood step of cytokinesis. It consists of the final cut of the intercellular bridge connecting the sister cells at the end of mitosis, and is thought to involve membrane trafficking as well as lipid and cytoskeleton remodelling. We previously identified the Rab35 GTPase as a regulator of a fast recycling endocytic pathway that is essential for post-furrowing cytokinesis stages.