Myosin XIK is a major player in cytoplasm dynamics and is regulated by two amino acids in its tail

It has recently been found that among the 17 Arabidopsis myosins, six (XIC, XIE, XIK, XI-I, MYA1, and MYA2) have a major role in the motility of Golgi bodies and mitochondria in Nicotiana benthamiana and Nicotiana tabacum. Here, the same dominant negative tail fragments were also found to arrest the movement of Gogi bodies when transiently expressed in Arabidopsis plants. However, when a Golgi marker was transiently expressed in plants knocked out in these myosins, its movement was dramatically inhibited only in the xik mutant. In addition, a tail fragment of myosin XIK could inhibit the movement of several post-Golgi organelles, such as the trans-Golgi network, pre-vacuolar compartment, and endosomes, as well as total cytoplasmic streaming, suggesting that myosin XIK is a major player in cytoplasm kinetics. However, no co-localization of myosin tails with the arrested organelles was observed. Several deletion truncations of the myosin XIK tail were generated to corroborate function with localization. All deletion mutants possessing an inhibitory effect on organelle movement exhibited a diffuse cytoplasmic distribution. Point mutations in the tail of myosin XIK revealed that Arg1368 and Arg1443 are essential for its activity. These residues correspond to Lys1706 and Lys1779 from mouse myosin Va, which mediate the inhibitory head–tail interaction in this myosin. Therefore, such an interaction might underlie the dominant negative effect of truncated plant myosin tails and explain the mislocalization with target organelles

Collisions of Cortical Microtubules with Membrane Associated Myosin VIII Tail

The distribution of myosin VIII ATM1 tail in association with the plasma membrane is often observed in coordination with that of cortical microtubules (MTs). The prevailing hypothesis is that coordination between the organization of cortical MTs and proteins in the membrane results from the inhibition of free lateral diffusion of the proteins by barriers formed by MTs. Since the positioning of myosin VIII tail in the membrane is relatively stable, we ask: can it affect the organization of MTs? Myosin VIII ATM1 tail co-localized with remorin 6.6, the position of which in the plasma membrane is also relatively stable. Overexpression of myosin VIII ATM1 tail led to a larger fraction of MTs with a lower rate of orientation dispersion. In addition, collisions between MTs and cortical structures labeled by ATM1 tail or remorin 6.6 were observed. Collisions between EB1 labeled MTs and ATM1 tail clusters led to four possible outcomes: 1—Passage of MTs through the cluster; 2—Decreased elongation rate; 3—Disengagement from the membrane followed by a change in direction; and 4—retraction. EB1 tracks became straighter in the presence of ATM1 tail. Taken together, collisions of MTs with ATM1 tail labeled structures can contribute to their coordinated organization

Down-Regulation of β-Catenin by Activated p53

β-Catenin is a cytoplasmic protein that participates in the assembly of cell-cell adherens junctions by binding cadherins to the actin cytoskeleton. In addition, it is a key component of the Wnt signaling pathway. Activation of this pathway triggers the accumulation of β-catenin in the nucleus, where it activates the transcription of target genes. Abnormal accumulation of β-catenin is characteristic of various types of cancer and is caused by mutations either in the adenomatous polyposis coli protein, which regulates β-catenin degradation, or in the β-catenin molecule itself. Aberrant accumulation of β-catenin in tumors is often associated with mutational inactivation of the p53 tumor suppressor. Here we show that overexpression of wild-type p53, by either transfection or DNA damage, down-regulates β-catenin in human and mouse cells. This effect was not obtained with transcriptionally inactive p53, including a common tumor-associated p53 mutant. The reduction in β-catenin level was accompanied by inhibition of its transactivation potential. The inhibitory effect of p53 on β-catenin is apparently mediated by the ubiquitin-proteasome system and requires an active glycogen synthase kinase 3β (GSK3β). Mutations in the N terminus of β-catenin which compromise its degradation by the proteasomes, overexpression of dominant-negative ΔF-β-TrCP, or inhibition of GSKβ activity all rendered β-catenin resistant to down-regulation by p53. These findings support the notion that there will be a selective pressure for the loss of wild-type p53 expression in cancers that are driven by excessive accumulation of β-catenin