Location matters: the endoplasmic reticulum and protein trafficking in dendrites

Ramírez, Omar; Härtel, Steffen; Couve, Andrés

doi:10.4067/s0716-97602011000100003

Cited by 11 publications

(4 citation statements)

References 54 publications

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“…The EE-RR peptides may bind each other because of hydrophobic interactions that result in the formation of intermolecular complexes. These molecular complexes of SomaGCaMP6f2 or So-maGCaMP7f may be sufficient to slow trafficking from the cell body (Ramı ´rez et al, 2011). In both cases, expression of these proteins did not alter active or passive membrane properties or the distribution of all endogenous channels that we examined.…”

Section: Discussionmentioning

confidence: 80%

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Shemesh

Linghu

Piatkevich

et al. 2020

Neuron

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Section: Discussionmentioning

confidence: 80%

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Shemesh

Linghu

Piatkevich

et al. 2020

Neuron

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“…ER in the proximal somatodendritic regions is mostly ribosome-rich while the distal dendritic regions mostly contain ribosome free tubular ER with occasional cisternae [23]. In general, along the dendrite length, the ER presents an uneven terrain of tubules with distinct microdomains [169].…”

Section: Er In Dendritesmentioning

confidence: 99%

“…Morphological changes are seen in dendrites and dendritic spines in hippocampus post traumatic brain injury and treatments [172]. The area occupied by dendritic ER corresponds to the number of spines or synapses in the particular dendritic segment [169]. Larger spines have the ER network reaching into their head region while the smaller ones have ER only until their neck, connected in both cases by a single tubule with rest of the ER network [23].…”

Section: Er In Dendritesmentioning

confidence: 99%

Morphological Heterogeneity of the Endoplasmic Reticulum within Neurons and Its Implications in Neurodegeneration

Sree

Parkkinen

Their

et al. 2021

Cells

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The endoplasmic reticulum (ER) is a multipurpose organelle comprising dynamic structural subdomains, such as ER sheets and tubules, serving to maintain protein, calcium, and lipid homeostasis. In neurons, the single ER is compartmentalized with a careful segregation of the structural subdomains in somatic and neurite (axodendritic) regions. The distribution and arrangement of these ER subdomains varies between different neuronal types. Mutations in ER membrane shaping proteins and morphological changes in the ER are associated with various neurodegenerative diseases implying significance of ER morphology in maintaining neuronal integrity. Specific neurons, such as the highly arborized dopaminergic neurons, are prone to stress and neurodegeneration. Differences in morphology and functionality of ER between the neurons may account for their varied sensitivity to stress and neurodegenerative changes. In this review, we explore the neuronal ER and discuss its distinct morphological attributes and specific functions. We hypothesize that morphological heterogeneity of the ER in neurons is an important factor that accounts for their selective susceptibility to neurodegeneration.

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“…The ER is constituted by an irregular network that effectively connects the whole neurons, from the soma to the distal dendrites, to the axon, and it even enters in synapses, playing a role in synaptic stabilization [17]. The presence of ER in dendrites correlates with the spine density, [18], and it acts as a reservoir of proteins in dendrites, [19] providing membrane proteins, such as glutamate receptors, in dendrites [20]. A 3DEM reconstruction of the SER in dendrites is shown in [21].…”

Section: Endoplasmic Reticulummentioning

confidence: 99%

Statistical laws of protein motion in neuronal dendritic trees

Sartori¹

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Neurons are cells with a highly complex morphology; their dendritic arbor spans up to thousands of micrometers. This extended arbor poses a challenge for the logistics of neuronal processes: mRNA, proteins, and organelles have to be transported to dendrites, hundreds of micrometers away from the soma. This thesis aims to calculate the minimum number of proteins needed to populate the dendritic trees for different scenarios. In chapter 2, I analyzed the ability of different mechanisms to populate the dendritic arbor. I started from the solution of the diffusion equation in Sec. 2.1, then I included the contribution of active transport in Sec. 2.2 and showed how it could have either the effect of increasing the effective diffusion coefficient or of introducing a bias in the diffusion process. In Sec. 2.3 I studied the spatial distribution of locally synthesized protein, accordingly with actively and passively transported mRNA. In Sec. 2.5, I derived the boundary condition for branches showing a qualitatively different behavior of surface and cytoplasmic proteins induced by the medium’s dimensionality in which they diffuse. In chapter 3, I introduced the concept of protein requirement, defined as the minimum number of proteins that the neuron needs to produce to provide at least one protein to each micrometer of the dendritic arbor. In Sec. 3.1, I derived the protein requirement for diffusive proteins for somatic translation and constant translation in the dendritic arbor. In Sec. 3.2, I analyzed numerically the protein requirement in the case of actively transported protein synthesized in the soma, and, in Sec. 3.3, in the case of actively transported proteins synthesized in the dendritic arbor. In Sec. 3.4, I analyzed the protein requirement of protein synthesized in the dendrite accordingly with the distribution of mRNA described in Sec. 3.3 and 3.2. In Sec. 3.5, I derived the protein requirement for a single branch and purely diffusive proteins. In chapter 4, I analyzed the relation between the radii of the three afferent dendrites in a branch, their length, and the diffusion length of a protein. In Sec. 4.1 I derived the optimal ratio between the radii of the daughter dendrites that minimizes the protein requirement. In Sec. 4.3 I introduced the 3/2− Rall Rule and in Sec. 4.5 its generalization. Finally, I used those rules to estimate the fraction of proteins diffusing away from and toward the soma. In chapter 5, I analyzed the radii distribution for three categories of neurons: cultured hippocampal neurons in Sec. 5.1, stomatogastric ganglia neuron in Sec. 5.2, and 3DEM reconstructed prefrontal pyramidal neurons in Sec. 5.3. For each of these three classes, I analyzed the distribution of radii, Rall exponents, and the probability ratio. For most of them, I found that the probability of a protein diffusing away from the soma is higher for surface proteins than for cytoplasmic ones. I quantified this with a parameter called surface bias. In Chapter 6, I analyzed the fluorescent ratio imaged by our collaborators Anne-Sophie Hafner, for a surface protein, GFP::Nlg, and a soluble one, GFP, in cultured hippocampal neurons, and I compared the fluorescent ratio with the probability ratio obtained in 5.1, finding that they are in good agreement. In chapter 7, I compared the real dendritic morphologies imaged by one of our collaborators Ali Karimi with the optimal branching rule obtained in Sec. 4.1 and I calculated the cost for not having optimal branching radii. Finally, in Chapter 8, I used the knowledge of the branching statistics gathered in 5.3 to simulate the protein profile on three different classes of neurons: pyramidal neurons, granule neuron, and Purkinje neurons. I compared the protein profile for surface and cytoplasmic neurons for each morphology for two different values of the diffusion length: λ = 109µm and λ = 473µm, both for optimized radii and symmetrical radii. I showed how the radii optimization reduces the protein requirement of a factor 10 4 for pyramidal neurons.

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Location matters: the endoplasmic reticulum and protein trafficking in dendrites

Cited by 11 publications

References 54 publications

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Morphological Heterogeneity of the Endoplasmic Reticulum within Neurons and Its Implications in Neurodegeneration

Statistical laws of protein motion in neuronal dendritic trees

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