imissyou419's version from 2016-12-20 16:29


Question Answer
Nucleolusregion of ribosome synthesis, involved in cell response to stress, assembly of signal recognition particles
Euchromatinareas of gene expression
Heterochromatinareas of gene silencing
Nuclear envelopemade up of 2 phospholipid bilayers (outer and inner) - outer is continuous with ER, inner is supported by nuclear lamina
Nuclear laminaprotein meshwork, mostly made up of lamins (IF in nucleus) and lamin associated proteins, connect to inner nuclear membrane and chromatin
Type A lamin codingall types encoded from alternate splicing of LMNA gene
Type B lamin codingencoded by 2 genes, LMNB1 and LMNB2
Where do you find Type A and B lamin in the nucleus?accumulate on inner membrane of nucleus, suggest they have role in nuclear structure, signalling
Type A lamin expressionhigher expression in mechanical type tissue -> skeletal and cardiac muscles; provide better structure for nuclei and in FIXED place
Type B lamin expressionmay be disposable but more highly expressed in undifferentiated cells (embryonic stem cells, blood cells); allow for more FLEXIBILITY
Lamin functionstructural support and shape to the nucleus, associate with chromosomes, mechanotransduction, regulate gene expression (basically signalling + support)
LINClinker of nucleoskeleton (lamins) and cytoskeleton (tubulin,actin, IF), affect signalling pathways and gene regulation
Signalling complex from PM to nucleusIntegrin -> actin -> Nesprin 1/2 -> SUN1 & SUN2 -> Lamin -> Chromatin
Emery-Dreifuss muscular dystrophyMutation in LINC genes including LMNA point mutation H222Y; muscle degeneration, weakness and atrophy; cardiac defect (type A found in cardiac + skeletal muscle)
Dunnigan-type familial partial lipodystrophyVarious missense mutations (change a.a.) in LMNA, adipose tissue redistribution, insulin resistant diabetes mellitus
Charcot-Marie-Tooth disease type 2B1Recessive mutation in LMNA, motor and sensory neuropathy, slight or absent reduction of nerve-conduction velocities (demyelination)
Hutchinson-Gilford progeria syndromeLMNA deletion, early onset aging, alopecia, fragile skin, atherosclerosis
Greenberg sketal dysplasiahomozygous mutation in genes encoding type B lamin, fatal before birth, significant skeletal abnormalities, fluid accumulation
Pelger-Huet anomalyHeterozygous mutation of the type B lamin gene
Lamin A or lamin C (Type A) is ____ in leukemias, lymphomas, breast cancer, colon cancer, gastric carcinoma, OVARIAN carcinomadownregulated, reduced expression of type A lamins -> more malleable nuclei, which could facilitate extravasation & invasion (metastasis) of malignant cell through narrow constrictions
Type A lamin is ___ in skin and OVARIAN cancersupregulated, higher lamin levels support the increased mechanical stress with solid tumors
Changes in lamin expression could affectproliferation (nuclear membrane has to breakdown), differentiation (by affecting gene expression in terms of signalling), EMT (requires nucleus to be malleable), migration


Question Answer
What types of movement are there to move molecules to nucleus?passive diffusion - molecules (< 40 kDa), ions; facilitated active transport molecules (>40 kDa)
Is nuclear pores evenly distributed?No, there are areas where there is more pores
Is the composition of proteins for nuclear pore the same between cell types?No, not ubiquitous composition of proteins b/w cell types, allowing for cell type specific transport
What is the composition of nuclear pores?membrane associated scaffold, central transport channel, cytoplasmic ring, nuclear ring, 8 filaments attach to each ring
Nucleoporinsnot ubiquitous composition of proteins between cell types, allowing for cell type specific transport, some components of the pore change in response to signals
Nuclear localization signalall basic residues allow for high binding affinity with acidic residues in nucleus for retention
Karyopherinssoluble carrier protein that facilitate active transport e.g. exportins and importins
How is the RAN gradient used for nucleus cytoplasm transport?IMPORT: Ran-GDP has high affinity for importin and causes transcription factor (NFAT) to be bound to complex (importinalpha/beta), translocate and get conversion of Ran-GDP to Ran-GTP which has low affinity and the transcription factor is released;

EXPORT: CRM1 has high affinity for NFAT when Ran-GTP binds to NFAT, translocate to cytoplasm, GTP is hydrolyzed and transcription factor is released
Brownian affinity gate modelmacromolecules that do not bind to NUPs do not diffuse across the NPC (MUST BIND TO NUPS TO GET ACROSS), diffusive movement of filamentous NUPs may contribute to this exclusion (filaments pushing things away), macromolecules that bind to NUPs increase their residence time at the entrance of the central tube, diffusion across NPCs is greatly facilitated (FG residues allow for binding of specific macromolecules)
Selective phase modellow-affinity inter-nucloeporin interactions mediated by phenylalanine-glycine (FG) repeats generate a highly hydrophobic environment in the NPC, repel inert molecules from entering the NPC, the transport-receptor-cargo complex (importin), owing to its interaction with FG-repeats, can partition into the hydrophobic central core of the NPC and permeate this barrier


Question Answer
Other ways ions get into nucleusnuclear chloride channel, Ca2+ ATPases, vacuolar H+-ATPases (rather than just passively diffuse through nuclear pores)
Why does progeria not affect the CNS?LMNA not expressed in neurons
How are NLS signatures different?recognize different regions of importin alpha, different importin alpha isoforms, recognized by specific importin beta family without importin alpha (similar in that they are all basic, different in way they interact with importin)