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1.  N-Cadherin, Spine Dynamics, and Synaptic Function 
Frontiers in Neuroscience  2008;2(2):168-175.
Dendritic spines are one-half (the postsynaptic half) of most excitatory synapses. Ever since the direct observation over a decade ago that spines can continually change size and shape, spine dynamics has been of great research interest, especially as a mechanism for structural synaptic plasticity. In concert with this ongoing spine dynamics, the stability of the synapse is also needed to allow continued, reliable synaptic communication. Various cell-adhesion molecules help to structurally stabilize a synapse and its proteins. Here, we review the effects of disrupting N-cadherin, a prominent trans-synaptic adhesion molecule, on spine dynamics, as reported in Mysore et al. (2007). We highlight the novel method adopted therein to reliably detect even subtle changes in fast and slow spine dynamics. We summarize the structural, functional, and molecular consequences of acute N-cadherin disruption, and tie them in, in a working model, with longer-term effects on spines and synapses reported in the literature.
doi:10.3389/neuro.01.035.2008
PMCID: PMC2622743  PMID: 19225589
spine dynamics; N-cadherin; structural constraints; measurement noise; hippocampus
2.  Effects of N-Cadherin Disruption on Spine Morphological Dynamics 
Structural changes at synapses are thought to be a key mechanism for the encoding of memories in the brain. Recent studies have shown that changes in the dynamic behavior of dendritic spines accompany bidirectional changes in synaptic plasticity, and that the disruption of structural constraints at synapses may play a mechanistic role in spine plasticity. While the prolonged disruption of N-cadherin, a key synaptic adhesion molecule, has been shown to alter spine morphology, little is known about the short-term regulation of spine morphological dynamics by N-cadherin. With time-lapse, confocal imaging in cultured hippocampal neurons, we examined the progression of structural changes in spines following an acute treatment with AHAVD, a peptide known to interfere with the function of N-cadherin. We characterized fast and slow timescale spine dynamics (minutes and hours, respectively) in the same population of spines. We show that N-cadherin disruption leads to enhanced spine motility and reduced length, followed by spine loss. The structural effects are accompanied by a loss of functional connectivity. Further, we demonstrate that early structural changes induced by AHAVD treatment, namely enhanced motility and reduced length, are indicators for later spine fate, i.e., spines with the former changes are more likely to be subsequently lost. Our results thus reveal the short-term regulation of synaptic structure by N-cadherin and suggest that some forms of morphological dynamics may be potential readouts for subsequent, stimulus-induced rewiring in neuronal networks.
doi:10.3389/neuro.03.001.2007
PMCID: PMC2525931  PMID: 18946519
spine dynamics; N-cadherin; motility; cell adhesion; structural constraints; hippocampus
3.  Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function 
The Journal of Cell Biology  2002;156(6):959-968.
Mutations in the human LIS1 gene cause type I lissencephaly, a severe brain developmental disease involving gross disorganization of cortical neurons. In lower eukaryotes, LIS1 participates in cytoplasmic dynein-mediated nuclear migration. We previously reported that mammalian LIS1 functions in cell division and coimmunoprecipitates with cytoplasmic dynein and dynactin. We also localized LIS1 to the cell cortex and kinetochores of mitotic cells, known sites of dynein action. We now find that the COOH-terminal WD repeat region of LIS1 is sufficient for kinetochore targeting. Overexpression of this domain or full-length LIS1 displaces CLIP-170 from this site without affecting dynein and other kinetochore markers. The NH2-terminal self-association domain of LIS1 displaces endogenous LIS1 from the kinetochore, with no effect on CLIP-170, dynein, and dynactin. Displacement of the latter proteins by dynamitin overexpression, however, removes LIS1, suggesting that LIS1 binds to the kinetochore through the motor protein complexes and may interact with them directly. We find that of 12 distinct dynein and dynactin subunits, the dynein heavy and intermediate chains, as well as dynamitin, interact with the WD repeat region of LIS1 in coexpression/coimmunoprecipitation and two-hybrid assays. Within the heavy chain, interactions are with the first AAA repeat, a site strongly implicated in motor function, and the NH2-terminal cargo-binding region. Together, our data suggest a novel role for LIS1 in mediating CLIP-170–dynein interactions and in coordinating dynein cargo-binding and motor activities.
doi:10.1083/jcb.200109046
PMCID: PMC2173479  PMID: 11889140
dynein; dynactin; LIS1; CLIP-170; kinetochores
4.  Polyploids require Bik1 for kinetochore–microtubule attachment 
The Journal of Cell Biology  2001;155(7):1173-1184.
The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore–MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics.
doi:10.1083/jcb.200108119
PMCID: PMC2199317  PMID: 11756471
kinetechore; microtubule; ploidy; Bik1; plus end–tracking protein

Results 1-4 (4)