Membrane Transport and Disease

Question 1

Simple diffusion

Answer 1

Small gases, water, lipophilic molecules

No transporters and no specificity

Question 2

Facilitated diffusion

Answer 2

Specificity
Requires transporter
Saturation kinetics observed
No direct Energy

Question 3

Ligate gated channels respond

Answer 3

Signaling molecule

Question 4

Open channels respond to

Answer 4

Local concnetrations of solutes

Question 5

Voltage-gated channels respond to

Answer 5

Membrane potential changes

Question 6

Channels responding to covalent modification typically

Answer 6

Phosphorylation

Question 7

Mechanosensitive channels respond to

Answer 7

Deformations in bilayer

Question 8

Aquaporins role, location, regulation

Answer 8

Water translocation
Differnet tissues
Exo/endocytosis

Question 9

Aquaporins exampel of

Answer 9

Mechano-sensitive channel

Question 10

Aquaporin sturcture

Answer 10

Alpha-helical homotetramers…hourglass shape

Question 11

NDI

Answer 11

Nephrogenic Diabetes insipidus

Question 12

Most common form of NDI

Answer 12

Defect in vasopressin receptor making kidney tubules unresponsive to vasopression (X-dominant)

Question 13

Other form of NDA

Answer 13

Defect in aquaporin-2 for water reabsorption (recessive)

Question 14

Symptoms of NDI

Answer 14

Large urine output, dehyration

Question 15

F class pump

Answer 15

H+ across inner mitochondrial membrane

Question 16

V class pump

Answer 16

H+ across endosomal/lysosomal mebrnae

Question 17

P class pump

Answer 17

H+, Na+, K+, Ca2+ across plasma membrane

Question 18

ABC class pumps

Answer 18

Found in plasma and intracellular membrnaes…catalyze influx of lipids, peptides, ions, and drugs

Question 19

Primary carriers

Answer 19

ATp or GTP driven

Question 20

Secondary carriers

Answer 20

Concentration driven

Question 21

Importance of nuclear pore membrane wrapping

Answer 21

Transport of membrane proteins back into nucleus from the ER

Question 22

Effective channel size of nuclear pore

Answer 22

9-26 nm

Question 23

Fast diffuson of nuclear pore

Answer 23

<5 kDa

Question 24

Slow diffusion of nuclear pore

Answer 24

6-50 kDa

Question 25

Active transport of nuclear pore

Answer 25

>50 kDa

Question 26

NLS

Answer 26

Signal for import...string of basic amino acids (+ charged)

Question 27

NES

Answer 27

Hydrophobic amino acids

Question 28

NRS

Answer 28

Tell to stay in the nucleus

Question 29

Nuclear recycling mechanism

Answer 29

Binding of calcineurium marks NES of NF-AT and activates import signal via dephosphorylation...once back inside the nucleus, calcineurium leaves, NF-AT rephosphorylated, and NES exposed

Question 30

What causes calcineurium to bind to NF-AT outside fo cell

Answer 30

High Calcium concentration

Question 31

Small G proteins activated and inactivated by

Answer 31

Activated by GEF (guanine-nucleotide-exchange-factor) | Inactivated by GAP (GTPase-activating-protein)

Question 32

GEF reaction

Answer 32

Removes GDP from Ras and replaces with GTP

Question 33

Movement of ____ drives active nuclear transport

Answer 33

Ran - small G-protein

Question 34

Ran-GTP/Ran-GDP locations

Answer 34

Ran-GTP - nucleus | Ran-GDP - cytosol

Question 35

Ran-GAP

Answer 35

Ran GTPase-activating protein...dephosphorylates the Ran-GTP complex in cytosol

Question 36

Ran-GEF

Answer 36

Ran gunaine nucleotide exchange factor (bound to chromatin) | Phosphorylates RAN-GDP in the nucleus

Question 37

Importin steps

Answer 37

Importin binds cargo protein with NLS Complex associates with fibrils and enters nucleus RanGTP binds importin inside nucleus and displaces cargo Importin and Ran-GTP exit nucleus Ran Binding Protein displaces RanGTP and importin is free RanGAP activates RanGTP and hydrolyses GTP RanGDP recycles to nucleus where RanGEF promotes exchange of GDP for GTP

Question 38

Export steps

Answer 38

``` Exportin binds target AND RanGTP Complex moves out Ran binding protein displaces RanGTp Exportin releases cargo RanGTP released from RanBP RanGAP activates RanGTP and hydrolyses Exportin and RanGDP back to nucleus RanGDP converted by to RanGTP by RanGEF ```

Question 39

ALS Very early symptoms

Answer 39

Fatigue, muscle weakness, poor concentration

Question 40

ALS early

Answer 40

Cramps, spasticity, limb onset, slurred or nasal speech, bulbar onset

Question 41

ALS late

Answer 41

Difficulty moving, dysphagia, dysarthia

Question 42

ALS terminal

Answer 42

Resp failure or penumonia

Question 43

Only small % of ALS is ____

Answer 43

inherited

Question 44

Only ALS therapy and what it does

Answer 44

Riluzole | Blocks voltage gated sodium channels to prevent glutamate release

Question 45

Most common mutation of ALS

Answer 45

C9orf72 (GGGGCC) hexanucleotide expansion

Question 46

ALS mutations of C9orf72

Answer 46

Haploinsufficiency due to reduced expression of gene copy on expanded repeat halotype RNA gain-of-function toxicity because of aggregates formed Abnormal bidirectional transcription of expanded repeat sequences followed by Non-AUG-initiated tranlation into aggregation prone proteins

Question 47

3 things the GGGGCC mutation does

Answer 47

1) Directly clog NPC 2) Bind to RanGAP preventing nuclear import 3) Abnormal form of tranlation to form toxic dipeptide rpeeat proteins (DPRs) that interphere with import through karyopherins