Physiology 3140A Lecture Notes - Lecture 1: Lamin B2, Nuclear Lamina, Nuclear Pore
22 May 2018
School
Department
Course
Professor
Physiology 3140
Dr. Pin
Lecture 1
Structure of the Nucleus
- Double plasma membrane (outer and inner membrane)
- Have nuclear pores
- Contains DNA
o Light parts: euchromatin (loosely packed – DNA is not
silenced)
o Dark parts: heterochromatin (tightly packed DNA – hard for
transcription factors to get in so that DNA is silenced)
- Nucleolus
o Where rRNA is made
o Involved in cell response to stress and signal recognition
Nuclear Envelope
- Made up of two phospholipid bilayers (outer and inner)
- The outer membrane is continuous with the endoplasmic reticulum
- It is important that the nucleus holds it structure and keeps the DNA organized
- Structural support on inner surface by the nuclear lamina
- How is this structure maintained?
Nuclear Lamin
- Protein meshwork
- Mostly made up of lamins and lamin associated proteins (LAP1, LAP2, emerin)
- Lamin and lamin associated proteins connect to the chromatin and the DNA
o Bc it helps keep them organized
o By keeping chromatin attached to the nuclear lamin, it helps keep it organized
- Its also associated with these nesprin (intermediate filaments) that extend all the way to the
cellular membrane
o So it can be a response to signaling pathways directly from cell membrane
- The pink intermediate filaments are the lamins
find more resources at oneclass.com
find more resources at oneclass.com
Lamins
- Type of intermediate filament found in the nucleus
- 2 types: A type and B type
- A-type – all types encoded from alternate splicing of the LMNA gene
- B-type – encoded by two genes, LMNB1 & LMNB2
- Both A type and B type lamins are found around the nuclear membrane
- Blue stain= DAPI (stains nucleus)
Lamin Function
- A-type lamins
o higher expression in mechanical type tissues (skeletal and cardiac muscle)
o more sturdy (give the nucleus a firmer structure)
- B-type lamins
o may be disposable bc not expressed in differentiated cells
o but for undifferentiated cells to get somewhere, they need to pass between cells so we
want the nucleus to not be firm so it can pass through places
o highly expressed in undifferentiated cells (embryonic stem cells)
o if undifferentiated cells want to get somewhere, they would want the nucleus to not be
so firm
o more flexible
- provide structural support and shape to the nucleus
- associate with chromosomes
o this can help with the signaling of transcription, coordination of cytoplasmic processes
and division
o ex: when you want to keep the chromatin organized when dividing the cell, by having
the lamina associated with the chromosomes, it helps keep the chromosomes organized
- can also help with transport
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find more resources at oneclass.com
o the nucleus is not always going to be in the middle of the cell, sometimes it will be
around
o lamins and LNC complex can associate with the cytoskeleton and motor proteins and
move nucleus around the cell
o ut can associate with the skeleton and motor proteins to more ____around
- associated with mechanotransduction
o when the cell undergoes mechanical stress, it can signal to the nucleus directly assist in
regulation of gene expression
- regulates gene expression
LINC
- run through the nuclear membrane and connects the lamin to the cytoskeleton of the cell
- LNC = Linker of nucleoskeleton and cytoskeleton
- Affects signaling pathways and gene transcription
- Lamins associate with sun1 and sun2 proteins that enter into the nuclear membrane
- These then associate with nesprin 1/2 which can move all the way and interact with the actin
cytoskeleton and integrins
- So this can act as a direct conduit from the plasma membrane to the DNA in signal transduction
- Signal from PM gets directly transduced in the nucleus without need of a signaling cascade
Laminopathies
- There are lots of diseases (laminopathies)associated with lamina
- Emery-muscular dystrophy
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Double plasma membrane (outer and inner membrane) Contains dna: light parts: euchromatin (loosely packed dna is not, dark parts: heterochromatin (tightly packed dna hard for transcription factors to get in so that dna is silenced) silenced) Involved in cell response to stress and signal recognition. Made up of two phospholipid bilayers (outer and inner) The outer membrane is continuous with the endoplasmic reticulum. It is important that the nucleus holds it structure and keeps the dna organized. Structural support on inner surface by the nuclear lamina. Mostly made up of lamins and lamin associated proteins (lap1, lap2, emerin) Lamin and lamin associated proteins connect to the chromatin and the dna: bc it helps keep them organized, by keeping chromatin attached to the nuclear lamin, it helps keep it organized. Its also associated with these nesprin (intermediate filaments) that extend all the way to the cellular membrane: so it can be a response to signaling pathways directly from cell membrane.
