Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.
Membrane-bound and membraneless organelles/biomolecular condensates ensure compartmentalization into functionally distinct units enabling proper organization of cellular processes. Membrane-bound organelles form dynamic contacts with each other to enable the exchange of molecules and to regulate organelle division and positioning in coordination with the cytoskeleton. Crosstalk between the cytoskeleton and dynamic membrane-bound organelles has more recently also been found to regulate cytoskeletal organization. Interestingly, recent work has revealed that, in addition, the cytoskeleton and membrane-bound organelles interact with cytoplasmic biomolecular condensates. The extent and relevance of these complex interactions are just beginning to emerge but may be important for cytoskeletal organization and organelle transport and remodeling. In this review, we highlight these emerging functions and emphasize the complex interplay of the cytoskeleton with these organelles. The crosstalk between membrane-bound organelles, biomolecular condensates and the cytoskeleton in highly polarized cells such as neurons could play essential roles in neuronal development, function and maintenance.
Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the ER and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule -lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule -lysosome contacts at a preaxonal region finely orchestrate axonal lysosome availability for proper neuronal function. KEYWORDSNeurons, axonal transport, lysosome, ER organization, ER tubules, kinesin-1, microtubules, pre-axonal region, lysosome motility and fission, P180. Özkan et al.Yet, it remains unclear how local ER organization regulates LE/ lysosome size and how this is linked to motor transfer and MT interaction at contact sites.Proper organization and transport of ER tubules and LEs/ lysosomes are crucial for neuronal development and function. ER tubules and LEs/ lysosomes are translocated from the soma into the axon by the kinesin-1 motor (Farías et al., 2017;Farías et al., 2019). Local availability of ER tubules instructs axon formation and regulates axonal synaptic vesicle cycling (Farías et al., 2019;Lindhout et al., 2019) and active transport of LEs/ lysosomes into the axon is required for proper clearance of faulty proteins and organelles located far away from the cell soma (Farías et al., 2017; Farfel-Becker et al., 2019). Interestingly, mutations in genes encoding ER-shaping proteins cause the neurodegenerative disease hereditary spastic paraplegia, in which aberrant lysosomes have been observed (Westrate et al., 2015; Allison et al., 2017;Lee and Blackstone, 2020). Therefore, it is important to understand how the organization of the ER and inter-organelle communication contribute to lysosome organization and local availability in neurons.Here, we show that ER shape regulates local lysosome availability in neurons, in which somatic ER tubules promote lysosome translocation into the axon. Disruption of somatic ER tubules causes accumulation of enlarged and less motile mature lysosomes in the soma due to impaired lysosome homofission. We find that ER tubule -lysosome contacts are enriched in a pre-axonal region. The MT-and kinesin-1-binding ER protein P180 is enriched and co-distributed with kinesin-1-decorated axonal MT tracks in the same pre-axonal region, where it promotes lysosome motility, fission and axonal translocation. Together, ...
Bu çalışmada, 7-14 yaşlar arasındaki çocuklara hitap eden resimli kitap, masal ve roman-öykü türündeki Türkçe çocuk kitaplarının 1967 yılına göre. 1997 yılında dil açısından nasıl bir değişim gösterdiği incelenmiştir. Bu amaçla. 1967 yılında yayımlanmış 24 ve 1997 yılında yayımlanmış 47 olmak üzere toplam 71 çocuk kitabı değerlendirilmiştir. Yapılan değerlendirmede anlatım bozukluğu, yazım kuralları, noktalama işaretleri, yabancı ve argo kelime kullanımı ile dizgi hataları temel ölçütler (kriterler) olarak alınmıştır. Araştırma sonucunda, çocuk kitaplarında 1997 yılında 1967 yılına göre, dil kullanım açısından olumlu bir değişim olduğu anlaşılmıştır.
Local mRNA translation in axons is critical for the spatial and temporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons, however how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with ER tubules in the axon in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation in an mRNA-dependent manner. Our results establish an important role for the axonal ER in localizing mRNA translation and in dynamically regulating the axonal proteome in response to neuronal stimuli.
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