Dynein and muskelin control myosin VI delivery towards the neuronal nucleus

Abstract

Highlights Myosin VI and muskelin are recruited to the neuronal nucleus Active cytoplasmic dynein is required for myosin VI and muskelin nuclear targeting Muskelin regulates myosin VI to dynein binding and myosin VI nuclear translocation Dynein mediates nuclear translocation of myosin VI during cLTP

Tubb3 expression levels are sensitive to neuronal activity changes and determine microtubule growth and kinesin-mediated transport

“…They are characterized by a dynamic microtubule cytoskeleton consisting of different tubulin isotypes [ 3 , 8 , 47 , 48 ], however it is barely understood whether activity changes induce changes in tubulin expression and whether a differential use of specific tubulin isotypes alters microtubule and/or transport function. In an initial experiment, we applied established chemical protocols to induce long-term potentiation (cLTP) to trigger a long-lasting increase in synaptic strength in cultured hippocampal neurons [ 38 , 39 , 49 ]. Using a fusion protein of the microtubule + TIP factor EB3 (EB3-Tomato), known to label growing microtubules [ 50 , 51 ], we found that increased synaptic strength leads to a significant increase in microtubule growth velocities, as compared to control conditions (Fig.…”

“…To induce cLTP in dissociated mouse hippocampal neurons, neurons transfected at DIV8-9 were subjected to cLTP induction 3 days post transfection. cLTP was induced by treatment with 50 µM Forskolin, 100 nM Rolipram and 100 µM Picrotoxin [ 38 , 39 ] (Tocris, Wiesbaden-Nordenstadt, Germany) for 10 min in Ringer solution without Mg 2+ (125 mM NaCl, 2,5 mM KCl, 3 mM CaCl 2 , 33 mM d -Glucose, 25 mM HEPES, pH 7.3) (all Sigma, Steinheim, Germany) at 37 °C in a humidified incubator with 5% CO 2 . Thereafter, neurons were washed once with warm PBS and for recovery from cLTP induction, neurons were incubated in Ringer solution containing Mg 2+ (125 mM NaCl, 2,5 mM KCl, 2 mM CaCl 2 , 33 mM d -Glucose, 1 mM MgCl 2 , 25 mM HEPES, pH 7.3).…”

A comprehensive analysis of MYO6 as a promising biomarker for diagnosis, prognosis, and immunity in clear cell renal cell carcinoma

“…MYO6 can be transcriptional regulated by p53 and stress signals, on the contrary, the low expression of MYO6 would affect the stability and activation of p53. In the past, a large number of studies ( 7 ) have proved that p53 is an important anticancer gene that causes cancer cells to undergo apoptosis, thereby preventing carcinogenesis, and plays an important role in the pathogenesis and treatment of cancer ( 8 ). Thus, we realize that MYO6 gene is closely related to cancer.…”

Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes

“…Suppression of muskelin is shown to alter the dynamics of focal adhesion assembly 1 and to disrupt stress fiber organization that critically depends on actomyosin contractility 2 . At the same time, muskelin depletion robustly promotes cell migration 2 – 4 and results in cells with enlarged perimeters caused by increased ruffling and formation of actin-containing protrusive edges 2 , 3 .…”

“…In neurons, muskelin has a predominantly cytoplasmic distribution, with a punctate expression pattern along axons and dendrites 4 , 5 . We recently demonstrated that muskelin associates with and modulates the bidirectional transport of cellular prion protein (PrP C ), a mechanism that contributes to accelerated prion disease onset in Mkln 1-null mice upon challenge with pathogenic prion 6 .…”