Peroxisome Membrane Proteins

Question 1

What is the PEX19 binding sequence that most proteins targeted to the peroxisome membrane contain

Answer 1

11mer helical peptides with invariant basic residues flanked by hydrophobic amino acids e.g. KVLRLLQYLARFLAV

Question 2

are peroxisome membrane targeting sequences cleaved

Answer 2

no as they are integral to the protein

Question 3

where is the signal sequence found for single span peroxisome membrane proteins

Answer 3

for N term anchored proteins the sequence is found in the Nterm+the first transmembrane domain and in C term anchored proteins it is found in the C term + 1st TM domain

Question 4

where is the signal sequence found for multi span peroxisome membrane proteins

Answer 4

At least 1 or 2 TM domains plus flanking regions comprise the signal sequence

Question 5

What is the evidence to suggest that there are different genetic requirements to import membrane proteins from matrix proteins

Answer 5

matrix import mutants are still able to effectively integrate membrane proteins

Question 6

which 3 proteins comprise the peroxisome membrane protein receptors

Answer 6

PEX3, 19 and 16

Question 7

what is the role of PEX3

Answer 7

it is a membrane receptor for PEX19

Question 8

what is the role of PEX19

Answer 8

It is the proposed chaperone for PMPs which is predominantly cytosolic. It bids newly synthesised peroxisomal proteins via its globular C terminal domain and binds PEX3 via its flexible Nterm

Question 9

how is binding of PMPs to PEX19 enhanced

Answer 9

by farnesylation of PEX19. this is also thought to enhance insertion

Question 10

what is the role of PEX16

Answer 10

potentially PEX3 receptor, plays a role in insertion or cats as a PMP receptor- the role is not clear but it is implicated in PMP import in mammals

Question 11

what family of proteins regulate peroxisome division

Answer 11

PEX11 family

Question 12

what is the role of PEX11 in peroxisome devision and how then is division facilitated

Answer 12

it binds the surface of peroxisomes and causes it to tubulate. Division factors which are dynamin GTPases are recruited which are involved in division

Question 13

How are peroxisomes inherited from mother to daughter cells in yeast

Answer 13

they move along the actin based skeleton in yeast and microtubules in mammals. In yeast they are anchored to actin by binding Imp1p. Imp2 acts as a receptor to recruit an isoform of myosin which can move the peroxisome along the actin into the daughter cell.

Question 14

what are the 3 models to describe where peroxisomes come from

Answer 14

derivation of the ER
autonomous organelles
hybrid model

Question 15

what does the model which suggests peroxisomes are derived from the ER outline

Answer 15

it suggests that peroxisomes are offshoots from the ER system. mRNA translated into peroxisome proteins were transported into the ER then into a vesicle and then budded off to form peroxisomes

Question 16

what was the evidence that peroxisomes derived from the ER

Answer 16

apparent physiscal connections/close proximity to the ER and cell fractionation studies in which ER and peroxisomal proteins were found in the same fraction

Question 17

what does the model which suggests peroxisomes are autonomous organelles outline

Answer 17

that we have always had peroxisomes and that peroxisomal proteins were targeted to small organelles which grew and could be divided and passed onto daughter cells

Question 18

what does the hybrid model for peroxisomal origin outline

Answer 18

it suggests that the ER does play a role however mutants that lack detectable peroxisomes can regain them when the missing gene product is supplied. PEX3 when first synthesised will first go to the ER and then to peroxisomes at which point peroxisomal import can occur.

Question 19

describe how scPEX15p is inserted into the ER and then transported to peroxisomes for insertion into the peroxisomal membrane

Answer 19

the complex called guided entry of tail anchored proteins (GET) facilitates insertion into the ER. vesicles containing scPex15p and scpex3p can be formed from ER in vitro which transport it to peroxisomes

Question 20

give an example of a PEX7 mutant disorder

Answer 20

RCDP (group B) causing growth defects, cataracts, epiphyseal calcifications etc. also results in low plasmalogens and high levels of phyantic acid

Question 21

give an example of a PEX7 mutant disorder

Answer 21

group A disorders e.g. Zellweger syndrome. results in loss of all matrix proteins causing severe neurological and hepatic dysfunction and ultimately early death. present with low levels of plasmalogens (ether linked lipids made in peroxisomes) and high levels of substrates which should be oxidised via beta oxidation of fatty acids such as VLCFA

Question 22

give an example of a disorder caused by mutation of an individual peroxisomal enzyme

Answer 22

X-linked adrenoleukodystrophy

Question 23

what is the result of PEX14 mutations in plants

Answer 23

defects in photorespiration, matrix protein import and b oxidation

Question 24

what is the result of PEX5 mutations in plants

Answer 24

defects in b oxidation

Question 25

what is the result of PEX10 mutations in plants

Answer 25

essential for embryo development.