Microtubules are one of the major cytoskeletal components of neurons, essential for many fundamental cellular and developmental processes, such as neuronal migration, polarity, and differentiation. ...Microtubules have been regarded as critical structures for stable neuronal morphology because they serve as tracks for long-distance transport, provide dynamic and mechanical functions, and control local signaling events. Establishment and maintenance of the neuronal microtubule architecture requires tight control over different dynamic parameters, such as microtubule number, length, distribution, orientations, and bundling. Recent genetic studies have identified mutations in a wide variety of tubulin isotypes and microtubule-related proteins in many of the major neurodevelopmental and neurodegenerative diseases. Here, we highlight the functions of the neuronal microtubule cytoskeleton, its architecture, and the way its organization and dynamics are shaped by microtubule-related proteins.
The structural organization and dynamic remodeling of the cytoskeleton contributes to all morphological and functional changes in neurons. Here, Kapitein and Hoogenraad review the functions of the neuronal microtubule cytoskeleton and the mechanisms that drive its organization and dynamics.
Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses and are major sites of information processing and storage in the ...brain. Changes in the shape and size of dendritic spines are correlated with the strength of excitatory synaptic connections and heavily depend on remodeling of its underlying actin cytoskeleton. Emerging evidence suggests that most signaling pathways linking synaptic activity to spine morphology influence local actin dynamics. Therefore, specific mechanisms of actin regulation are integral to the formation, maturation, and plasticity of dendritic spines and to learning and memory.
Microtubules are cytoskeletal filaments that are intrinsically polarized, with two structurally and functionally distinct ends, the plus end and the minus end. Over the last decade, numerous studies ...have shown that microtubule plus-end dynamics play an important role in many vital cellular processes and are controlled by numerous factors, such as microtubule plus-end-tracking proteins (+TIPs). In contrast, the cellular machinery that controls the behavior and organization of microtubule minus ends remains one of the least well-understood facets of the microtubule cytoskeleton. The recent characterization of the CAMSAP/Patronin/Nezha family members as specific ‘minus-end-targeting proteins’ (‘-TIPs’) has provided important new insights into the mechanisms governing minus-end dynamics. Here, we review the current state of knowledge on how microtubule minus ends are controlled and how minus-end regulators contribute to non-centrosomal microtubule organization and function during cell division, migration and differentiation.
Akhmanova and Hoogenraad review our current understanding of how microtubule minus ends are controlled and how minus-end regulators contribute to non-centrosomal microtubule organization and function during cell division, migration and differentiation.
In neurons, the distinct molecular composition of axons and dendrites is established through polarized targeting mechanisms, but it is currently unclear how nonpolarized cargoes, such as ...mitochondria, become uniformly distributed over these specialized neuronal compartments. Here, we show that TRAK family adaptor proteins, TRAK1 and TRAK2, which link mitochondria to microtubule-based motors, are required for axonal and dendritic mitochondrial motility and utilize different transport machineries to steer mitochondria into axons and dendrites. TRAK1 binds to both kinesin-1 and dynein/dynactin, is prominently localized in axons, and is needed for normal axon outgrowth, whereas TRAK2 predominantly interacts with dynein/dynactin, is more abundantly present in dendrites, and is required for dendritic development. These functional differences follow from their distinct conformations: TRAK2 preferentially adopts a head-to-tail interaction, which interferes with kinesin-1 binding and axonal transport. Our study demonstrates how the molecular interplay between bidirectional adaptor proteins and distinct microtubule-based motors drives polarized mitochondrial transport.
► Kinesin-1 and dynein drive mitochondrial transport to axons and dendrites ► TRAK1 binds to both kinesin-1 and dynein/dynactin and is localized in axons ► TRAK2 predominantly interacts with dynein/dynactin and is present in dendrites ► TRAK2 backfolding inhibits kinesin-1 binding and controls mitochondrial transport
van Spronsen et al. show that mitochondria utilize different machineries to steer their transport into axons and dendrites. The molecular interplay between mitochondrial adaptor protein family TRAK/Milton and distinct microtubule-based motors drives polarized mitochondrial transport.
Excitatory (glutamatergic) synapses in the mammalian brain are usually situated on dendritic spines, a postsynaptic microcompartment that also harbors organelles involved in protein synthesis, ...membrane trafficking, and calcium metabolism. The postsynaptic membrane contains a high concentration of glutamate receptors, associated signaling proteins, and cytoskeletal elements, all assembled by a variety of scaffold proteins into an organized structure called the postsynaptic density (PSD). A complex machine made of hundreds of distinct proteins, the PSD dynamically changes its structure and composition during development and in response to synaptic activity. The molecular size of the PSD and the stoichiometry of many major constituents have been recently measured. The structures of some intact PSD proteins, as well as the spatial arrangement of several proteins within the PSD, have been determined at low resolution by electron microscopy. On the basis of such studies, a more quantitative and geometrically realistic view of PSD architecture is emerging.
Proper positioning of organelles by cytoskeleton-based motor proteins underlies cellular events such as signalling, polarization and growth. For many organelles, however, the precise connection ...between position and function has remained unclear, because strategies to control intracellular organelle positioning with spatiotemporal precision are lacking. Here we establish optical control of intracellular transport by using light-sensitive heterodimerization to recruit specific cytoskeletal motor proteins (kinesin, dynein or myosin) to selected cargoes. We demonstrate that the motility of peroxisomes, recycling endosomes and mitochondria can be locally and repeatedly induced or stopped, allowing rapid organelle repositioning. We applied this approach in primary rat hippocampal neurons to test how local positioning of recycling endosomes contributes to axon outgrowth and found that dynein-driven removal of endosomes from axonal growth cones reversibly suppressed axon growth, whereas kinesin-driven endosome enrichment enhanced growth. Our strategy for optogenetic control of organelle positioning will be widely applicable to explore site-specific organelle functions in different model systems.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In neurons, the polarized distribution of vesicles and other cellular materials is established through molecular motors that steer selective transport between axons and dendrites. It is currently ...unclear whether interactions between kinesin motors and microtubule‐binding proteins can steer polarized transport. By screening all 45 kinesin family members, we systematically addressed which kinesin motors can translocate cargo in living cells and drive polarized transport in hippocampal neurons. While the majority of kinesin motors transport cargo selectively into axons, we identified five members of the kinesin‐3 (KIF1) and kinesin‐4 (KIF21) subfamily that can also target dendrites. We found that microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) labels a subset of dendritic microtubules and is required for KIF1‐dependent dense‐core vesicles (DCVs) trafficking into dendrites and dendrite development. Our study demonstrates that microtubule‐binding proteins can provide local signals for specific kinesin motors to drive polarized cargo transport.
Synopsis
While kinesin motors selectively move into axons, kinesin‐3 and kinesin‐4 can also target dendrites. Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) provides local cues to steer polarized movement of kinesin‐3 into dendrites.
Twenty‐three members of the kinesin subfamily are able to transport cargo in living cells.
Kinesin‐3 (KIF1) and kinesin‐4 (KIF21) family members target both axon and dendrites.
DCLK1 associates with a specific subset of microtubules in dendrites.
DCLK1 is required for KIF1‐mediated dense‐core vesicle trafficking into dendrites.
While kinesin motors selectively move into axons, kinesin‐3 and kinesin‐4 can also target dendrites. Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) provides local cues to steer polarized movement of kinesin‐3 into dendrites.
Transport of different intracellular cargoes along cytoskeleton filaments is essential for the morphogenesis and function of a broad variety of eukaryotic cells. Intracellular transport is mediated ...by cytoskeletal motors including myosin, kinesin, and dynein, which are typically linked to various cargoes by adaptor proteins. Recent studies suggest that adaptor proteins can also act as essential transport cofactors, which control motor activity and coordination. Characterization of the evolutionary conserved Bicaudal D (BICD) family of dynein adaptor proteins has provided important insights into the fundamental mechanisms governing cargo trafficking. This review highlights the advances in the current understanding of how BICD adaptors regulate microtubule-based transport and how they contribute to developmental processes and human disease.
Broad- and fine-leaved woody species respond to seasonal changes from wet to dry season differently. For example, broad-leaved species shed their leaves earlier, while fine-leaved species, especially ...acacias retain green foliage well into the dry season. These differences are expected to result in variation in selection of broad- and fine-leaved woody species as browse by free-ranging goats. We tested the hypothesis that free-ranging goats select broad-leaved woody species more than fine-leaved species during wet (growth) season and fine-leaved woody species more than broad-leaved species during dry season. In addition, we tested if broad- and fine-leaved woody species had different foliar dry matter digestibility and chemical composition (crude protein, neutral detergent fibre, acid detergent fibre, total phenolics and condensed tannins concentration). Free-ranging goats were observed foraging on broad- and fine-leaved woody species over a two-year period (2014 and 2015) during three seasons: early wet (October/November), late wet (February/March) and dry (May/June). Ivlev's selectivity or Jacob's index (Ei) was calculated for five woody species (two broad-leaved and three fine-leaved) browsed by goats during wet and dry season. Jacob's selectivity index was higher for broad-leaved (Ziziphus mucronata and Searsia (Rhus) tenuinervis) than fine-leaved woody species (Acacia nilotica, Acacia karroo and Dichrostachys cinerea) during wet season. However, the trend was reversed during dry season with fine-leaved species having higher Jacob's selectivity index than broad-leaved species. Leaf dry matter digestibility and chemical composition was similar between broad- and fine-leaved woody species throughout the year. We conclude that goats selected broad-leaved woody species during wet season when browse was plentiful and then switched to fine-leaved species which retained leaves during dry season.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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