70 research outputs found
ROP GTPase-Dependent Actin Microfilaments Promote PIN1 Polarization by Localized Inhibition of Clathrin-Dependent Endocytosis
A study in leaf epidermal pavement cells reveals that auxin activation of a Rho-like GTPase from plants induces inhibition of endocytosis through the clathrin-mediated pathway by regulating the accumulation of cortical F-actin
The Mechanochemistry of Endocytosis
An integrated theoretical model reveals how the chemical and the mechanical aspects of endocytosis are coordinated coherently in yeast cells, driving progression through the endocytic pathway and ensuring efficient vesicle scission in vivo
Distinct Dynamics of Endocytic Clathrin-Coated Pits and Coated Plaques
Here we classify endocytic structures at the adherent (bottom) surface of many cells in culture into shorter-lived coated pits and longer-lived coated plaques which internalize by different mechanisms
Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins
A genome-scale specificity and interaction map for yeast SH3 domain-containing proteins reveal how family members show selective binding to target proteins and predicts the dynamic localization of new candidate endocytosis proteins
NESH Regulates Dendritic Spine Morphology and Synapse Formation
Background: Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown. Methodology/Principal Findings: NESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dendritic spines, suggesting this interaction is important for the maturation of dendritic spines. Conclusions/Significance: NESH is a novel F-actin binding protein that likely plays important roles in the regulation o
Synapse Geometry and Receptor Dynamics Modulate Synaptic Strength
Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD) and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity
Expression of the Salmonella Spp. Virulence Factor SifA in Yeast Alters Rho1 Activity on Peroxisomes
SifA is a virulence protein required for assembly and tubulation of a modified phagosome that promotes Salmonella replication. We show that SifA expressed in yeast induces membrane invagination during peroxisome proliferation and requires functional Rho1p. This is consistent with SifA ability to interact with RhoA and the fact that it is a GEF structural homologue
Long-Term Relationships between Synaptic Tenacity, Synaptic Remodeling, and Network Activity
Long term time-lapse imaging reveals that individual synapses undergo significant structural remodeling not only when driven by activity, but also when network activity is absent, raising questions about how reliably individual synapses maintain connections
Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression
Changes in synaptic efficacies need to be long-lasting in order to serve as a
substrate for memory. Experimentally, synaptic plasticity exhibits phases
covering the induction of long-term potentiation and depression (LTP/LTD) during
the early phase of synaptic plasticity, the setting of synaptic tags, a trigger
process for protein synthesis, and a slow transition leading to synaptic
consolidation during the late phase of synaptic plasticity. We present a
mathematical model that describes these different phases of synaptic plasticity.
The model explains a large body of experimental data on synaptic tagging and
capture, cross-tagging, and the late phases of LTP and LTD. Moreover, the model
accounts for the dependence of LTP and LTD induction on voltage and presynaptic
stimulation frequency. The stabilization of potentiated synapses during the
transition from early to late LTP occurs by protein synthesis dynamics that are
shared by groups of synapses. The functional consequence of this shared process
is that previously stabilized patterns of strong or weak synapses onto the same
postsynaptic neuron are well protected against later changes induced by LTP/LTD
protocols at individual synapses
Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways
Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also
between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles,
while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi
apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics
of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main
routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder
content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups
contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some
of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more
disordered (,23%) than the other two, COPI (,9%) and COPII (,8%). We show that this structural phenomenon enhances
the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other
two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its
prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest
capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific
functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for
protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of
structural disorder in vesicle trafficking and suggest major roles for this structural property in shaping the differences of
evolutionary adaptability in the three routes
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