Final Exam Short Answers Flashcards
What problem do surface receptors solve?
Specificity and selectivity: Different surface receptors have specific binding sites that recognize and bind to particular ligands or signals with high selectivity. This specificity ensures that cells can distinguish between different signals and respond appropriately.
How do surface receptors solve the problem identified?
Ligand binding studies: Extensive research has been conducted to characterize the binding affinities and specificities of various ligands (e.g., hormones, neurotransmitters, growth factors) to their respective surface receptors. These studies have shown that specific receptors bind to their cognate ligands with high affinity and selectivity while exhibiting low or negligible binding to other ligands. Cellular responses: Cells can respond differently to different ligands that bind to distinct surface receptors, even when those ligands share structural similarities. This specificity of cellular responses is a direct consequence of the selective activation of distinct signaling pathways by different surface receptors.
Identify two benefits or advantages to having multi-level signal transduction pathways.
Multi-level signal transduction pathways provide numerous advantages, including signal amplification, regulation, signal integration, specificity of responses, spatial and temporal control, and robustness. These pathways allow for the amplification of signals from different levels, enabling even low levels of extracellular signals to trigger substantial cellular responses. They also offer multiple points of regulation and control, allowing for fine-tuning and precise control of cellular responses.
Complex signal transduction pathways can integrate multiple input signals from different sources, allowing cells to respond appropriately to complex environmental cues. Different levels of a signal transduction pathway can activate distinct downstream effectors or transcription factors, enabling cells to generate specific and diverse responses to the same initial stimulus.
Spatial and temporal control is also possible through multi-level signal transduction pathways, allowing for precise spatial and temporal control of cellular processes. Additionally, having multiple levels in a signal transduction pathway ensures reliable transmission and prevents disruption by perturbations or mutations in a single component of the pathway.
From what germ layer do neural cells derive?
During embryonic development, the ectoderm germ layer forms the basis for neural cells. The blastula, a hollow ball of cells, undergoes gastrulation, forming three distinct germ layers: ectoderm, mesoderm, and endoderm. The ectoderm is the outermost germ layer, containing the nervous system, epidermis, sensory organs, and parts of the mouth and anus. During early embryonic development, a portion of the ectoderm thickens and forms the neural plate, which folds inward to form the neural tube. The neural tube gives rise to the brain and spinal cord, while neural crest cells migrate from the tube and differentiate into various neural and non-neural cell types. Thus, neural cells, including neurons and glial cells, originate from the ectoderm germ layer during early embryonic development.
Describe the process of AP patterning in Drosophila
The anteroposterior (AP) patterning in Drosophila melanogaster, the fruit fly, is a crucial developmental process that establishes the body plan along the anterior-posterior axis. This process involves the expression of maternal effect genes, segmentation genes, and signaling pathways. Maternal effect genes, such as bicoid, Nanos, and caudal, create concentration gradients within the egg, providing positional information along the AP axis. The bicoid gene establishes the anterior pattern, regulating the expression of gap genes, which in turn control the expression of pair-rule and segment polarity genes. The nanos gene establishes the posterior pattern, counteracting the effects of the Bicoid gradient at the posterior end. Gap genes, such as hunchback, Krüppel, knirps, and giant, are expressed in broad domains along the AP axis, regulated by maternal effect gene gradients and cross-regulatory interactions. Pair-rule genes, such as even-skipped, fushi tarazu, and hairy, are expressed in a striped pattern along the AP axis, regulated by gap genes and their interactions. Segment polarity genes, such as engrailed, wingless, and hedgehog, are expressed in specific regions within each segment, establishing the polarity and identity of each segment, and leading to distinct structures within each segment.
Describe the consequence of BMP binding to its receptors. How does this change after the BMP antagonism and FGF binding to its receptors?
BMP (Bone Morphogenetic Protein) binding to its receptors initiates the Smad signaling pathway, phosphorylating and activating Smad transcription factors, which regulate cell differentiation, proliferation, and patterning. BMP antagonists, such as Noggin, Chordin, and Follistatin, inhibit BMPs’ interaction with BMP receptors, leading to changes in cell differentiation, patterning, and development. FGF binding to its receptors initiates the MAPK signaling pathway and other downstream cascades, regulating processes like cell proliferation, migration, differentiation, and patterning. FGF can interact with and modulate the BMP signaling pathway through mechanisms like the regulation of BMP antagonists and cross-talk between signaling pathways. The interplay between BMP signaling, BMP antagonism, and FGF signaling is crucial for regulating developmental processes, tissue patterning, and cell fate determination. The specific consequences of these signaling events can vary depending on the developmental stage, tissue type, and overall cellular and molecular context.
Early signaling for synaptogenesis by Wnts is dependent or independent transcription? How do we know this?
Independent because Wnt signaling is local. Blocking ribosomes doesn’t inflict any change.
Identify and briefly define four phases of axon growth
encounter substrate: substrate approaches signal
Protrusion: filopodia and lamellopodia extend from the growth cone
Engorgement: filopodia and lamellopodia in actin framework to extend further into the growth cone
Consolidation: the final step where filopodia begins exploration of the environment
Describe the activation/deactivation process of small g proteins (be precise and feel free to diagram – just remember to label and explain)
Activation:
* Ligand binding to cell surface receptors triggers GDP/GTP exchange factor (GEF) activation.
* GEFs catalyze the exchange of GDP bound to the small G protein with GTP.
* GTP binding induces a conformational change in the small G protein, leading to its activation
Deactivation:
* GTPase-activating proteins (GAPs) facilitate the hydrolysis of GTP to GDP.
* This hydrolysis reduces the affinity of the small G protein for its effectors, leading to deactivation.
* The GDP-bound form of the small G protein has a lower affinity for effector proteins and returns to its inactive state until the next activation cycle
Identify and briefly describe three of the six basic mechanisms of axon guidance
Extracellular matrix adhesion: growth-promoting molecules in the extracellular matrix
Cell surface adhesion: cell surface molecules on neural cell
Fasciculation: a growing axon encounters another axon from a “pioneer” neuron and tracks along it
Wnts are important for synaptogenesis in development; do they play a role in synaptic maintenance/loss in adults? How do we know?
- Synaptogenic factors are ideally suited to modulate synaptic stability. Indeed, Wnt signaling has now been demonstrated to regulate synaptic maintenance in mature neurons.
- Dkk1 rapidly induces the delocalization of pre and postsynaptic components in mature and stable hippocampal synapses.
- This effect is accompanied by a reduced number of SV recycling sites These findings provide evidence that endogenous Wnt signaling is required for synaptic maintenance diseases
What seems to be the most important for the selection of the neurite to become the axon? Describe some evidence for this.
Neurite outgrowth: the neurite that is the longest becomes the axon
Evidence: severing
* If the longest projection is cut shorter, it will not become the axon
* Neurite stains as tau before severing
* Taxol is a naturally occurring compound that binds to and stabilizes microtubules, preventing their depolymerization.
Describe the wnt pathway in early synaptogenesis and its consequences with a focus on the presynaptic side. Describe how this pathway overlaps with and how it differs from the canonical pathway, all the proteins involved, and what functions those proteins serve
The Wnt Signaling Pathway in Early Synaptogenesis
The Wnt pathway is crucial in early synaptogenesis, regulating presynaptic development and function. It is involved in various aspects of neuronal development, including axon guidance, dendritic morphogenesis, and synapse formation. The Wnt pathway primarily regulates the assembly and function of the presynaptic terminal. The Wnt pathway promotes synaptic vesicle clustering and active zone assembly, modulating neurotransmitter release, and regulating presynaptic protein synthesis. The non-canonical Wnt pathway involved in synaptogenesis diverges from the canonical pathway and does not involve β-catenin stabilization and nuclear translocation. Wnt ligands, Frizzled receptors, Dishevelled proteins, CAMK2, GSK3β, and PAR proteins are involved in the Wnt pathway. The Wnt pathway also influences postsynaptic development, including dendritic spine morphogenesis and synaptic receptor clustering.
Describe the wnt pathway in early synaptogenesis and its consequences with a focus on the postsynaptic side. Describe how this pathway overlaps with and how it differs from the canonical pathway, all the proteins involved, and what functions those proteins serve
The Wnt signaling pathway is a crucial component of early synaptogenesis, regulating postsynaptic development and function. It overlaps with the canonical Wnt/β-catenin pathway in its initial steps but diverges and involves distinct proteins and mechanisms on the postsynaptic side. The Wnt pathway is involved in the formation, maturation, and maintenance of dendritic spines, which are the primary sites of excitatory synaptic input on postsynaptic neurons. It also regulates the clustering and localization of neurotransmitter receptors, such as AMPA and NMDA receptors, at the postsynaptic density (PSD). The Wnt pathway can modulate local protein synthesis at the postsynaptic site, which is essential for synaptic plasticity and long-term potentiation (LTP).
The Wnt pathway has similarities with the canonical Wnt/β-catenin pathway, with the initial steps involving the binding of Wnt ligands to Frizzled receptors and the recruitment of Dishevelled (Dvl) proteins. However, on the postsynaptic side, the pathway diverges from the canonical Wnt/β-catenin pathway and does not involve β-catenin stabilization and nuclear translocation.
Key proteins involved in the Wnt pathway include Wnt ligands, Frizzled receptors, Dishevelled, Rac1, RhoA, JNK, PSD-95, and Homer, which regulate processes such as actin cytoskeleton dynamics, synaptic receptor localization, and postsynaptic protein synthesis.
Thoroughly describe the consequence of Delta binding its receptor. Be sure to discuss the consequences of the signal in terms of the larger system, describe the full pathway, and give context.
The Notch signaling pathway, initiated by the binding of Delta to its receptor Notch, is a crucial process in the development of neural and non-neural tissues. It involves a cascade of events, including receptor-ligand interaction, proteolytic cleavages, nuclear translocation of the Notch intracellular domain (NICD), and the activation of target genes through transcriptional regulation. Delta is a transmembrane ligand that binds to the Notch receptor on neighboring cells, triggering a series of proteolytic cleavages that release the Notch intracellular domain (NICD). The NICD translocates to the nucleus, where it forms a transcriptional activator complex with the DNA-binding protein CSL and other co-activators. This complex binds to specific DNA sequences and activates the expression of target genes, including the Hairy/Enhancer of split (Hes) and Hes-related (Hrt/Hey/Hesr) families of transcriptional repressors.
Notch signaling plays a crucial role in neural development, regulating the balance between neurogenesis and gliogenesis, establishing boundaries between different cell populations, and maintaining stem cell populations. This pathway operates in a context-dependent manner, interacting with other signaling pathways and transcriptional networks to precisely coordinate various developmental processes.
