Intracellular Compartments and Protein Transport

Study Notes

Three main protein transport pathways: nuclear pores, membrane transport, vesicle transport
Nuclear import requires a nuclear localization signal (NLS) and importin; size limit is approximately 60kDa (550 amino acids) for passive diffusion
Ran GTPase is crucial; GTP form is primarily in the nucleus, releasing imported proteins upon binding
mRNA export differs from protein export; it doesn't use Ran GTPase but relies on cap-binding proteins
Ribosomes bind to the ER via signal-recognition particle (SRP) for protein secretion targeting
SRP binds signal peptide, docks at SRP receptor; protein translocates across ER membrane
Clathrin-mediated endocytosis involves adaptin, clathrin, and dynamin
Exocytosis uses SNAREs (v-SNARE on vesicle, t-SNARE on target) and Rab GTPase
Glycosylation occurs in the ER, attaching carbohydrate chains to asparagine residues on proteins
Golgi apparatus has cis (nucleus-facing) and trans (cell edge-facing) regions; modifies proteins and synthesizes sphingolipids
Lysosomes maintain low pH via H+ pumps, activating enzymes
Transcytosis is the process of moving large molecules across cells without direct channel transport

Signaling types include endocrine (hormones, long-distance), paracrine (local), autocrine (self-targeting), and juxtacrine (contact-dependent)
Cell-surface receptors are for hydrophilic molecules; intracellular receptors for small, hydrophobic molecules.
Signaling outcomes can include cell survival, growth, division, differentiation, or death
Kinases add phosphates; phosphatases remove them from proteins; GTP-binding proteins act as molecular switches.
Receptor Tyrosine Kinase (RTK) signaling: ligand binding causes dimerization, kinase activation, and autophosphorylation, leading to Ras-MAPK pathways(growth/division) and PI3-K/Akt pathways(survival/metabolism)
G protein-coupled receptor (GPCR) signaling: ligand binding activates heterotrimeric G protein; key pathways include PKA activation (affecting glycogen breakdown, gene expression, Ca2+ release)
Other signaling types include NO signaling (diffusing gas), Notch signaling (contact-dependent, development-focused), steroid signaling(intracellular receptors)
SH2 domains recognize phosphorylated tyrosine residues on signaling proteins.

Cytoskeleton types include microtubules (a/β-tubulin dimers, dynamic, 13 protofilaments), actin filaments (ATP-dependent), and intermediate filaments (nonpolar, providing support)
Microtubules function in intracellular transport and cell division; structures like lamellipodia/filopodia allow for cell movement
Actin filaments interact with integrins at the cell membrane
Intermediate filaments (e.g., keratin and nuclear lamins) provide structural support
Microtubules exhibit dynamic instability, growing at the + end with GTP-tubulin and shrinking when GTP is hydrolyzed.
Motor proteins (kinesin and dynein) carry cargo along microtubules
Cilia have a 9+2 arrangement; dynein motors produce sliding for movement
Rho GTPases (e.g., Rho, Rac, Cdc42) regulate actin organization, impacting cell shape and movement