Polarity leads to a shift in tubulin modification and microtubule organization. In unpolarized epithelial cells, detyrosinated microtubules point to the spreading edge, but in polarized cells, acetylated microtubules point to the apical domain. In both cases the modified microtubules are oriented to support cargo transport to areas of high need.
Neurons are specialized cells with a polarized geometry and several distinct subdomains that require specific complements of proteins. Delivery of transmembrane proteins requires vesicle transport, which is mediated by molecular motor proteins. The myosin V family of motor proteins mediates transport to the barbed end of actin filaments, and little is known about the vesicles bound by myosin V in neurons. We developed a novel strategy to visualize myosin V‐labeled vesicles in cultured hippocampal neurons and systematically characterized the vesicle populations labeled by myosin Va and Vb. We find that both myosins bind vesicles that are polarized to the somatodendritic domain where they undergo bidirectional long‐range transport. A series of two‐color imaging experiments showed that myosin V specifically colocalized with two different vesicle populations: vesicles labeled with the transferrin receptor and vesicles labeled by low‐density lipoprotein receptor. Finally, coexpression with Kinesin‐3 family members found that myosin V binds vesicles concurrently with KIF13A or KIF13B, supporting the hypothesis that coregulation of kinesins and myosin V on vesicles is likely to play an important role in neuronal vesicle transport. We anticipate that this new assay will be applicable in a broad range of cell types to determine the function of myosin V motor proteins.
Curcumin is a natural polyphenol that exhibits remarkable
antioxidant
and anti-inflammatory activities; however, its clinical application
is limited in part by its physiological instability. Here, we report
the synthesis of curcumin-derived polyesters that release curcumin
upon hydrolytic degradation to improve curcumin stability and solubility
in physiological conditions. Curcumin was incorporated in the polymer
backbone by a one-pot condensation polymerization in the presence
of sebacoyl chloride and polyethylene glycol (PEG, M
n
= 1 kDa). The thermal and mechanical
properties, surface wettability, self-assembly behavior, and drug-release
kinetics all depend sensitively on the mole percentage of curcumin
incorporated in these statistical copolymers. Curcumin release was
triggered by the hydrolysis of phenolic esters on the polymer backbone,
which was confirmed using a PEGylated curcumin model compound, which
represented a putative repeating unit within the polymer. The release
rate of curcumin was controlled by the hydrophilicity of the polymers.
Burst release (2 days) and extended release (>8 weeks) can be achieved
from the same polymer depending on curcumin content in the copolymer.
The materials can quench free radicals for at least 8 weeks and protect
primary neurons from oxidative stress in vitro. Further, these copolymer
materials could be processed into both thin films and self-assembled
particles, depending on the solvent-based casting conditions. Finally,
we envision that these materials may have potential for neural tissue
engineering application, where antioxidant release can mitigate oxidative
stress and the inflammatory response following neural injury.
Neurons are polarized cells that require accurate membrane trafficking to maintain distinct protein complements at dendritic and axonal membranes. The Kinesin-3 family members KIF13A and KIF13B are thought to mediate dendrite-selective transport, but the mechanism by which they are recruited to polarized vesicles and the differences in the specific trafficking role of each KIF13 have not been defined. We performed live-cell imaging in cultured hippocampal neurons and found that KIF13A is a dedicated dendrite-selective kinesin. KIF13B confers two different transport modes, both dendrite- and axon-selective transport. Both KIF13s are maintained at the trans-Golgi network by interactions with the heterotetrameric adaptor protein complex AP-1. Interference with KIF13 binding to AP-1 resulted in disruptions to both dendrite- and axon- selective trafficking. We conclude that AP-1 is the molecular link between the sorting of polarized cargoes into vesicles and the recruitment of kinesins that confer polarized transport.
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