{"cells":[{"metadata":{},"cell_type":"markdown","source":"<h1 style=\"border:2px solid Purple;text-align:center\">Domain Understanding</h1>"},{"metadata":{},"cell_type":"markdown","source":"**As usual, I have created this notebook which focuses on the domain knowledge of the problem i.e. subcellular protein localization patterns.**"},{"metadata":{},"cell_type":"markdown","source":"**Reading this notebook will give the reader a thorough understanding of the problem domain. After reading the notebook one can go ahead and start solving the problem.**"},{"metadata":{},"cell_type":"markdown","source":"# Please don't forget to upvote if you like the content :)"},{"metadata":{},"cell_type":"markdown","source":"# Protein Localization"},{"metadata":{},"cell_type":"markdown","source":"In order for subcellular processes to be carried out within defined compartments or cellular regions, mechanisms must exist to ensure the required protein components are present at the sites and at an adequate concentration. The accumulation of a protein at a given site is known as protein localization."},{"metadata":{},"cell_type":"markdown","source":"![](https://www.mechanobio.info/wp-content/uploads/2017/06/co-translational-targeting-of-proteins-destined-for-secretion-membrane-insertion.jpg)"},{"metadata":{},"cell_type":"markdown","source":"Protein recruitment is essentially a form of protein recognition, made possible by the presence of specific amino-acid sequences within the protein structure. For example, many membrane bound proteins carry signal peptides that are recognized by signal receptors that guide them to the target site. The nuclear localization signal is one such example. Proteins that are destined for the endoplasmic reticulum also carry a signal peptide."},{"metadata":{},"cell_type":"markdown","source":"In other cases proteins may carry a signal patch. This usually consists of about 30 amino acids that are not present in a linear sequence, but are in close spatial proximity in the 3-dimensional space.\n\nInterestingly, the organization of a cell, and its various regions, do play a role in directing the recruitment of proteins to a given site. For example, in epithelial cells, which are polarized, protein composition at the apical membrane is very different from that at the basolateral membrane. This is achieved through the recognition of distinct signal sequences that target proteins to each of these regions. For example, apical membrane proteins are very often anchored to GPI (glycophosphatidylinositol) while basolateral proteins have diLeu (N,N-Dimethyl Leucine) or tyrosine amino acid based signature sequences "},{"metadata":{},"cell_type":"markdown","source":"Cytosolic proteins that are associated with the plasma membranes are often localized based on their interaction with membrane lipids such as the phosphoinositides. Phosphatidylinositol 4,5 bisphosphate (PIP2) is the most abundant phosphoinositide in mammalian cells. PIP2 is enriched in certain regions on the membrane, and due to its ability to interact with the PH (pleckstrin homology) domains of proteins; it can locally recruit proteins possessing such domains. FERM domain containing proteins, that link actin with the membrane, can also interact with PIP2. Another closely related phosphoinositide, Phosphatidylinositol 3,4,5 triphosphate (PIP3) may also be enriched in certain regions of the plasma membrane. The enrichment of PIP3 has been shown to accumulate at tips of neurons thus inducing cell polarization and axon formation. It is also suspected to induce local actin depolymerization in Dictyostelium cells and influence cell migration although other studies in neutrophils have indicated its role is in actin polymerization "},{"metadata":{},"cell_type":"markdown","source":"# Directed Delivery of Components"},{"metadata":{},"cell_type":"markdown","source":"Protein localization can result from the recognition of passively diffusing soluble proteins or protein complexes; however, this may not guarantee a sufficient concentration of components to maintain a given process. This can impede its completion, particularly when carried out in regions with a limited cytoplasmic volume, such as the tip of a filopodia, or when components are rapidly turned over.\n\nA more efficient way of maintaining the concentration of protein components is by their directed delivery via the cytoskeletal network.\n\nThe cytoskeleton, which is comprised of actin filaments and microtubules, spans the entire cell and connects the plasma membrane to the nucleus and other organelles. These filaments perform many purposes, from providing structural support to the cell, to generating the forces required for cell translocation. They may also serve as ‘tracks’ on which motor proteins can translocate as they carry cargo from one location to another; analogous to a freight train transporting cargo along a network of railway tracks.\n\nDelivery of components is primarily facilitated by ATP/GTP driven molecular motors such as myosin V or myosin X, Kinesin or Dynein. These proteins, or homologs of them, have been observed in a multitude of cell types, including yeast, plant and animal cells. The molecular motors dynein and kinesin walk on microtubules while myosin walks on actin filaments. Expectedly, these motors walk in a unidirectional manner, although not necessarily in the same direction as each other.\n\n"},{"metadata":{},"cell_type":"markdown","source":"# Communication Pathways\n\n\nWith different processes being carried out in separate subcellular compartments, organized across different regions of the cell, intracellular communication is paramount. Such communication, which is described in greater detail under ‘cell signaling’ allows cells to maintain the concentration of specific proteins and within the correct regions, depending on the requirements of a given process or cell state. This ultimately ensures individual compartments function efficiently, and enables one subcellular process to drive another. This ultimately allows a cell to facilitate its primary functions in an efficient and coherent manner.\n\nSignaling pathways may carry a signal that originates from outside a cell or from within various compartments and usually involves the translocation of ions, solutes, proteins and secondary messengers.\n\nAll cells have surface receptors and other proteins to facilitate sensing of signals from the extracellular environment. These signals can be in the form of ions, small molecules, peptides, shear stress, mechanical forces, heat, etc. Once the signal is sensed by the surface receptor, it is transmitted to the cytoplasm usually by means of conformational change in the receptor or change in its phosphorylation status on the cytosolic side. This in turn triggers a downstream signaling cascade, which very often culminates in the nucleus. The signal usually results in change in gene expression profile of cells, assisting them to respond to the stimulus.\n\n"},{"metadata":{},"cell_type":"markdown","source":"# Labelled Locations inside the cell"},{"metadata":{},"cell_type":"markdown","source":"**Now, we will move on to learning about the 18 different location inside the cells which are image labels in this problem.**\n\n**I will focus only on the structure of the location inside the cell because that's what relevant for us in this problem.**"},{"metadata":{},"cell_type":"markdown","source":"1. Nucleoplasm\n2. Nuclear membrane\n3. Nucleoli\n4. Nucleoli fibrillar center\n5. Nuclear speckles\n6. Nuclear bodies\n7. Endoplasmic reticulum\n8. Golgi apparatus\n9. Intermediate filaments\n10. Actin filaments\n11. Microtubules\n12. Mitotic spindle\n13. Centrosome\n14. Plasma membrane\n15. Mitochondria\n16. Aggresome\n17. Cytosol\n18. Vesicles and punctate cytosolic patterns"},{"metadata":{},"cell_type":"markdown","source":"You will all (except Vesicles and punctate cytosolic patterns) the labeled locations inside the two diagrams given below."},{"metadata":{},"cell_type":"markdown","source":"![](https://upload.wikimedia.org/wikipedia/commons/5/55/Figure_04_03_01a.png)"},{"metadata":{},"cell_type":"markdown","source":"![](https://upload.wikimedia.org/wikipedia/commons/4/4b/Cell-organelles-labeled.png)"}],"metadata":{"kernelspec":{"language":"python","display_name":"Python 3","name":"python3"},"language_info":{"pygments_lexer":"ipython3","nbconvert_exporter":"python","version":"3.6.4","file_extension":".py","codemirror_mode":{"name":"ipython","version":3},"name":"python","mimetype":"text/x-python"}},"nbformat":4,"nbformat_minor":4}