The function of organelles is intimately associated with rapid changes in membrane shape. By exerting force on membranes, the cytoskeleton and its associated motors have an important role in membrane remodelling. Actin and myosin 1 have been implicated in the invagination of the plasma membrane during endocytosis. However, whether myosin 1 and actin contribute to the membrane deformation that gives rise to the formation of post-Golgi carriers is unknown. Here we report that myosin 1b regulates the actin-dependent post-Golgi traffic of cargo, generates force that controls the assembly of F-actin foci and, together with the actin cytoskeleton, promotes the formation of tubules at the TGN. Our results provide evidence that actin and myosin 1 regulate organelle shape and uncover an important function for myosin 1b in the initiation of post-Golgi carrier formation by regulating actin assembly and remodelling TGN membranes.
The sense of taste comprises at least five distinct qualities: sweet, bitter, sour, salty, and umami, the taste of glutamate. For bitter, sweet, and umami compounds, taste signaling is initiated by binding of tastants to G-protein-coupled receptors in specialized epithelial cells located in the taste buds, leading to the activation of signal transduction cascades. ␣-Gustducin, a taste cell-expressed G-protein ␣ subunit closely related to the ␣-transducins, is a key mediator of sweet and bitter tastes. ␣-Gustducin knock-out (KO) mice have greatly diminished, but not entirely abolished, responses to many bitter and sweet compounds. We set out to determine whether ␣-gustducin also mediates umami taste and whether rod ␣-transducin (␣ t-rod ), which is also expressed in taste receptor cells, plays a role in any of the taste responses that remain in ␣-gustducin KO mice. Behavioral tests and taste nerve recordings of single and double KO mice lacking ␣-gustducin and/or ␣ t-rod confirmed the involvement of ␣-gustducin in bitter (quinine and denatonium) and sweet (sucrose and SC45647) taste and demonstrated the involvement of ␣-gustducin in umami [monosodium glutamate (MSG), monopotassium glutamate (MPG), and inosine monophosphate (IMP)] taste as well. We found that ␣ t-rod played no role in taste responses to the salty, bitter, and sweet compounds tested or to IMP but was involved in the umami taste of MSG and MPG. Umami detection involving ␣-gustducin and ␣ t-rod occurs in anteriorly placed taste buds, however taste cells at the back of the tongue respond to umami compounds independently of these two G-protein subunits.
Highlights d A complex HER2 + breast cancer ecosystem is reconstituted and quantitatively described d The effects of the drug trastuzumab (Herceptin) are directly visualized ex vivo d Trastuzumab promotes long cancer-immune interactions and an ADCC immune response d Trastuzumab and CAFs have antagonist immunomodulation effects
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