Signaling to the microtubule cytoskeleton: An unconventional role for <scp>C</scp>a<scp>MKII</scp>

McVicker, Derrick P.; Millette, Matthew M.; Dent, Erik W.

doi:10.1002/dneu.22227

Cited by 28 publications

(21 citation statements)

References 80 publications

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“…Of importance, polymerizing MTs must be recruited into specific dendritic spines rather than stochastically polymerizing into any spine. This recruitment of MTs into spines involves N -methyl- d -aspartate–dependent calcium influx, signaling cascades resulting in actin polymerization, and interaction of MT +TIP proteins (EB3) with actin-associated proteins in the spine neck (drebrin) and head (p140Cap; Jaworski et al , 2009; Merriam et al , 2011, 2013; McVicker et al , 2015). Further research will be required to determine whether other proteins associated with actin–MT interactions are involved in MT entry of spines.…”

Section: How Do Microtubules Enter Spines?mentioning

confidence: 99%

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

Dent

2017

MBoC

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117

104

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Microtubules (MTs) are cytoskeletal polymers composed of repeating subunits of tubulin that are ubiquitously expressed in eukaryotic cells. They undergo a stochastic process of polymerization and depolymerization from their plus ends termed dynamic instability. MT dynamics is an ongoing process in all cell types and has been the target for the development of several useful anticancer drugs, which compromise rapidly dividing cells. Recent studies also suggest that MT dynamics may be particularly important in neurons, which develop a highly polarized morphology, consisting of a single axon and multiple dendrites that persist throughout adulthood. MTs are especially dynamic in dendrites and have recently been shown to polymerize directly into dendritic spines, the postsynaptic compartment of excitatory neurons in the CNS. These transient polymerization events into dendritic spines have been demonstrated to play important roles in synaptic plasticity in cultured neurons. Recent studies also suggest that MT dynamics in the adult brain function in the essential process of learning and memory and may be compromised in degenerative diseases, such as Alzheimer’s disease. This raises the possibility of targeting MT dynamics in the design of new therapeutic agents.

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Section: How Do Microtubules Enter Spines?mentioning

confidence: 99%

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

Dent

2017

MBoC

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117

104

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“…formins (McVicker et al, 2015;Henty-Ridilla et al, 2016), and it will be interesting to test a potential role for the FMA in modulating F-actin dynamics.…”

Section: Mechanism Of Germ Plasm Distal Compactionmentioning

confidence: 99%

Slow calcium waves mediate furrow microtubule reorganization and germ plasm compaction in the early zebrafish embryo

et al. 2018

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Zebrafish germ plasm ribonucleoparticles (RNPs) become recruited to furrows of early zebrafish embryos through their association with astral microtubules ends. During the initiation of cytokinesis, microtubules are remodeled into a furrow microtubule array (FMA), which is thought to be analogous to the mammalian midbody involved in membrane abscission. During furrow maturation, RNPs and FMA tubules transition from their original distribution along the furrow to enrichments at the furrow distal ends, which facilitates germ plasm mass compaction. We show that mutants exhibit reduced furrow-associated slow calcium waves (SCWs), caused at least in part by defective enrichment of calcium stores. RNP and FMA distal enrichment mirrors the medial-to-distal polarity of SCWs, and inhibition of calcium release or downstream mediators such as Calmodulin affects RNP and FMA distal enrichment. Blastomeres with reduced or lacking SCWs, such as early blastomeres in mutants and wild-type blastomeres at later stages, exhibit medially bundling microtubules similar to midbodies in other cell types. Our data indicate that SCWs provide medial-to-distal directionality along the furrow to facilitate germ plasm RNP enrichment at the furrow ends.

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“…Alternatively or in addition, effects on the MT skeleton may also be mediated via calcium/calmodulin‐dependent kinase II, which has a key role as a decoder of local Ca 2+ signals and regulator of neuronal plasticity (McVicker et al . ). Interestingly, calcium/calmodulin‐dependent kinase II shows a transient enrichment coinciding with Ca 2+ transients where it interacts with MTs (Lemieux et al .…”

Section: Tau‐independent Mechanisms Of Mt Regulation In Admentioning

confidence: 97%

Microtubule dynamics and the neurodegenerative triad of Alzheimer's disease: The hidden connection

Brandt

Bakota

2017

Journal of Neurochemistry

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Alzheimer's disease (AD) is the most common neurodegenerative disorder and is, on a histopathological level, characterized by the presence of extracellular amyloid plaques composed of the protein fragment Ab, and intracellular neurofibrillary tangles, which contain the microtubule-associated protein tau in a hyperphosphorylated state. In AD defects in microtubule (MT) assembly and organization have also been reported; however, it is unclear whether MT abnormalities have a causal and early role in the disease process or represent a common end point downstream of the neurodegenerative cascade. Recent evidence indicates that microtubule-stabilizing drugs prevent axonopathy in animal models of tauopathies and reverse Ab-induced loss of synaptic connectivity in an ex vivo model of amyloidosis. This could suggest that MT dysfunction connects some of the degenerative events and provides a useful target to simultaneously prevent several neurodegenerative processes in AD. Here, we describe how changes in the structure and dynamics of MTs are involved in the different aspects of the neurodegenerative triad of AD. We discuss evidence that MTs are affected both by tau-dependent and tau-independent mechanisms but appear to be regulated in a distinct way in different neuronal compartments. We argue that modulation of MT dynamics could be of potential benefit but needs to be precisely controlled in a cell and compartment-specific manner to avoid harmful side effects.

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Signaling to the microtubule cytoskeleton: An unconventional role for CaMKII

Cited by 28 publications

References 80 publications

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

Slow calcium waves mediate furrow microtubule reorganization and germ plasm compaction in the early zebrafish embryo

Microtubule dynamics and the neurodegenerative triad of Alzheimer's disease: The hidden connection

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