19. Cell Trafficking and Protein Localization
TLDRThis script covers the trafficking of proteins within cells after they are synthesized. It discusses how targeting sequences in proteins or post-translational modifications determine if proteins will be transported to various organelles like the nucleus or mitochondria, remain in the cytoplasm, or be secreted from the cell. It also explains how proteins are directed to be secreted through association with the endomembrane system before being transported via vesicles to the plasma membrane. Signaling and diseases associated with mislocalization are introduced briefly at the end.
Takeaways
- 😊 Trafficking is the process of getting proteins and other molecules to the right place in the cell for proper function
- 👨🔬 50% of proteins made in the cytoplasm end up in other destinations like organelles, cell surface or secreted
- 🚚 Sequences in proteins act as barcodes to target them to destinations like the nucleus, mitochondria or peroxisomes
- 🔬 Bioinformatics can identify targeting sequences even if they are not obvious by eye
- ⚙️ Enzymes can post-translationally modify proteins to change their localization on demand
- 🚪 Nuclear pores allow transport between nucleus and cytoplasm using nuclear localization sequences
- 🚆 Alternating positive and negative charges target proteins to mitochondria through protein channels
- 📦 The endomembrane system transports proteins destined for secretion or display on the plasma membrane
- ♻️ Vesicles carry proteins through stages of the endomembrane system to eventually reach the cell exterior
- 🧬 Information for targeting comes from the genomic DNA sequence, even if cryptic at first
Q & A
What is cellular trafficking and what role does it play in cells?
-Cellular trafficking refers to the transport of molecules within cells to specific destinations. It ensures proteins end up where they are needed so the cell can carry out critical functions like division, signaling, etc.
What are the main mechanisms for protein trafficking in cells?
-The main mechanisms are: 1) Targeting sequences that are part of the protein sequence and act like barcodes, sending proteins to specific locales. 2) Post-translational modifications that occur after the protein is made and change its destination.
How does a nuclear localization sequence allow proteins to enter the nucleus?
-A nuclear localization sequence (NLS) is a short sequence of basic amino acids. It binds to importin proteins which then escort the cargo through the nuclear pore complex into the nucleus.
What triggers the transport of proteins with a mitochondrial localization sequence into the mitochondria?
-The mitochondrial localization sequence associates with a protein channel in the mitochondrial membrane. Binding triggers the channel to open, allowing import of the protein.
How are proteins destined for areas outside the cytoplasm made?
-These proteins have a 20 amino acid signal sequence that causes ribosomes to dock on the ER membrane. Proteins are directly synthesized into the ER rather than being released into the cytoplasm.
What is the purpose of vesicle transport through the endomembrane system?
-Vesicles carry membrane-associated proteins through the various compartments of the endomembrane system to their final destination, either displayed on the cell surface or secreted extracellularly.
How is the orientation of membrane proteins determined as they are made?
-Membrane proteins are synthesized with their amino terminus first into the ER lumen. As synthesis continues, transmembrane domains span the lipid bilayer so parts end up inside and outside the cell.
Why might diseases be associated with protein mislocalization?
-If proteins are not transported to the proper location in the cell, they cannot carry out their normal function. This disruption of cellular processes can lead to disease.
When is the targeting information for protein localization first encoded?
-The genomic DNA sequence contains encoding for targeting sequences or sites of post-translational modification guiding protein destination. This information may be spliced in the RNA.
How can fluorescent proteins be used to study protein trafficking?
-Tagging proteins with fluorescent markers allows real-time visualization of their transport within the cell upon a trigger stimulus using cellular imaging techniques.
Outlines
🧬 Overview of cellular trafficking and signaling
Paragraph 1 introduces the upcoming lectures on cellular trafficking and signaling. It mentions a news brief project for students to work on related to research in life sciences and engineering. The instructor is interested in cool topics at the interface of life sciences and engineering.
🚚 Cellular trafficking transports molecules to destinations
Paragraph 2 explains cellular trafficking as the process of transporting molecules like proteins, nucleic acids and sugars to specific destinations within the cell where they can carry out their functions. Even single-celled organisms need to receive signals and respond.
🌟 Imaging techniques visualize subcellular structures
Paragraph 3 discusses how fluorescent proteins and cellular imaging techniques allow real-time observation of dynamics and processes within cell structures and organelles.
📦 Targeting sequences and modifications direct trafficking
Paragraph 4 explains the two key mechanisms for protein trafficking - using targeting sequences that are part of the protein sequence which act as barcodes, and post-translational modifications which change proteins on demand to rapidly alter their destiny.
🔀 Lipidation inserts proteins into membranes
Paragraph 5 focuses on lipidation, a type of post-translational modification, which attaches a hydrophobic lipid group to render a protein lipophilic so that it inserts into a membrane for quicker trafficking.
🚪 Nuclear localization sequences cross the nuclear pore
Paragraph 6 discusses nuclear localization sequences (NLS), short basic amino acid sequences that mark proteins for transport into the nucleus through nuclear pores with the help of import proteins.
⚛️ Mitochondrial transport unfolds proteins
Paragraph 7 covers mitochondrial localization sequences (MLS) with alternating charges, which bind proteins to a closed channel in the mitochondrial membrane, triggering the channel to open, unfold and transport the protein inside.
🛳 Endomembrane system secretes extracellular proteins
Paragraphs 8-9 explain how proteins destined for secretion outside the cell have an N-terminal signal peptide that makes ribosomes dock onto the ER membrane and translate proteins directly into the endomembrane system for extracellular transport via vesicles.
🚹 Multi-pass membrane proteins assemble sideways
Paragraph 10 diagrams the complex biogenesis of multi-transmembrane proteins, where transmembrane domains get inserted sideways into the ER membrane and shuttle through the endomembrane system to the plasma membrane.
Mindmap
Keywords
💡trafficking
💡localization sequence
💡post-translational modification
💡importin
💡mitochondrial localization sequence
💡signal peptide
💡endoplasmic reticulum
💡vesicle
💡translocon
💡lipidation
Highlights
Trafficking is the process of transporting proteins to specific locations within or outside of the cell
Proteins are trafficked using targeting sequences encoded in the protein or through post-translational modifications that alter the protein's destination
Nuclear localization sequences (NLS) allow proteins to enter the nucleus by binding to import proteins that escort them through the nuclear pores
Mitochondrial localization sequences (MLS) bind to protein channels in the mitochondrial membrane to open them and allow proteins to enter
Mislocalization of proteins is associated with many diseases in cells
Lipidation attaches hydrophobic lipid groups to proteins to target them to cellular membranes
Phosphorylation and ubiquitination are other important post-translational modifications for protein trafficking
Proteins destined for secretion have signal sequences that cause ribosomes to dock on the ER membrane and translate them into the ER
The endomembrane system transports vesicles containing proteins through the Golgi apparatus to the cell surface or for secretion
Membrane proteins have domains that span the membrane with specific orientations of their N- and C-termini
Information for targeting sequences is encoded in the genomic DNA
Splicing can regulate inclusion or exclusion of targeting sequences like signal peptides
Fluorescently labeled proteins are used to study trafficking and localization in living cells
Bioinformatics helps identify targeting sequences and localization signals
Nuclear pores allow selective transport between the nucleus and cytoplasm
Transcripts
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