细胞生物学-endomembrane system内膜系统、蛋白质分选膜运输

Chapter

9Endomembrane

System,

ProteinSorting

And

Membrane

Traffic内膜系统、蛋白质分选、膜Lecture

1（

:By：）OUTLINEIntroductionEndoplasmic

ReticulumGolgi

complexLysosomesSecretory

and

EndocytosisThe

Mechanism

of

Vesicula

TransportMembrane-bound

organelle(膜结合细胞器)：organelles

or

compartments

that

possess

the

membranestructureCytoplasmic

membrane

system(细胞质膜系统)：organelles

are

correlate

with

cytoplasmic

membrane

about

biogenesis(在生物发生上与质膜相关的细胞器)Endomembrane

system(内膜系统)：membranous

organelles

within

the

cytoplasm

which

are

interrelated

instructures,functionsandoccurrence.(结构、功能、发生密切相关的内膜结构)：nuclear

membrane,

endoplasmic

reticulum,

Golgi

complex,

lysosomes,endosomes,

vacuoles,

vesicles.9.1.1

Membrane-bound

Organelleand

Endomembrane

system The

characteristicsof

endomembrane

systemDynamic,

interconnected

networkpathways

:biosynthetic

pathwaysecretory

pathway(

途径)endocytic

pathway(内吞途径) Biological

Meanings

OfEndomembrane

System区室化动态9.1.2 Protein

Sorting

蛋白质分选Protein ing

or

proteinsortingWHEN

and

HOWProtein

translocation----回答

“when”co-translational

translocation(共翻译转运)

一边

一边转运post-translational

translocation(翻译后转运)

先

再转运(1)

co-translational

translocationMembrane-bound

ribosome(2)

post-translational

translocationFree

ribosome(1)Through

nuclear

poreAcross

membraneBy

vesicleMechanisms

OfProteining蛋白质分选的三种机制-----回答“how”nuclear

porevesicleacrossmembraneSorting

Signal

directs

the

newly

madeprotein

to

a

proper

destination与生俱来的三种信号序列信号加工信号定位信号▲核定位信号▲引导肽▲信号肽1.

Transport

through

nuclear

poreProteins

bound

for

the

Nucleus

；

synthesized

by

free

ribosomes

in

cytosolNuclear

localization

signal

(核定位信号,NLS) VS.

nuclearimport

receptor

protein(核输入蛋白)nuclearlocalizationsignal,

NLSnuclear

import

receptorprotein2.

Transport

across

membraneProteins

bound

for oplasmic

reticulum,mitochondrion,

chloroplast

and

peroxisome;synthesized

by

free

ribosomes

in

cytosolLeading

peptide

（引导肽）

VS.protein

translocators

（蛋白转运蛋白）3.

Transport

by

vesicleProteins

moving

from

one

compartment

to

another

oroutside

of

cellsynthesized

by

membrane-bound

ribosomes

in

cytosolSecretory

protein:

Signal

peptide

信号肽

RER

COPⅡ

coated

vesicle

Golgi

complexclathrin

coated

vesicle

outside

of

cell9.2

Endoplasmic

reticulum

(ER)18971945,Garnier found“kinoplasm

动质”Port confirmed

ER

under

EM••1940

~60

era,

focus

on

structure

researchAfter

70

era,

focus

on

function

research9.2.1

Morphology

and

ChemicalComposition

morphologyShape:tubules管状,vesicles

泡状and

sacs

扁平network

of囊状that

areinterconnected

;thickness

is

5-6

nm;Two

surface

两个面：luminal

surface

or

cisternal

surface(潴泡面）cytoplasmic

surface

（胞质溶胶面）ER is

the

largest

organelle

in

most

eukaryoticcells.Its

membrane

may

account

for

about

half

of

allcell

membrane

system.the

space

enclosed

by

the

ER

may

representabout

10%

of

the

total

cell

volume.

chemical

composition

andenzymesMade

up

of

protein

and

lipidphospholipid(磷脂)protein30%~40%60%~70%Marker

Enzyme(标志酶):glucose

6-phosphatase(葡萄糖-6-磷酸酶)9.2.1内质网的类型Rough

endoplasmic

reticulum

(RER)扁平潴泡为多，

蛋白、多种膜蛋白、酶蛋白Smooth

endoplasmic

reticulum

(SER)常为小的管状和小的泡状结构。广泛存在与多种细胞中。特殊类型的内质网微粒体(microsome)肌质网(sarcoplasmic

reticulum)9.2.2

Main

Functions

of

SERglycogenolysis

andrelease

of

glucose(糖原分解与释放)Synthesis

of

lipids

and

transport(脂

与转运))Synthesis

of

steroid

hormones(类固醇激素Detoxification

in

the

liver

cell(肝细胞解毒)Regulate

Ca2+concentration(调节钙离子浓度)1.

glycogenolysis

and

release

of

glucose2.

Synthesis

of

lipids

and

transportSynthesis（

）SER

cytoplasmic

surfaceflip（翻转）翻转酶的作用transport（转运）vesicles

and

phospholipid

transfer

protein脂酰辅酶A磷酸甘油磷脂酸甘油二脂卵磷脂磷脂的mitochondrion,chloroplast

andperoxisome①transport

vesicle(小泡)Golgi

complex(高复合体)Lysosome(溶酶体)Cell

membrane②phospholipid

transfer

protein(PLTP，磷脂转运蛋白)磷脂的转运磷脂交换蛋白的作用3.

Synthesis

of

steroid

hormone类固醇激素(STH)Adrenal

cell(肾上腺细胞)、interstitial

cell(睾丸间质细胞,

又称

细胞Leydig

cell)、luteal

cells(

细胞)Synthesis

of

STH:acetyl

CoA

Cholesterol

steroid

hormone30步4.

Detoxification

in

the

liver

cellSER

contains

abundant

oxygenases(氧化酶),such

as

cytochrome

P450s（细胞色素P450）、NADH-cytochrome

C

redu e

(NADH-细胞色素还原酶),etc,混合功能的氧化酶(mixed-function

oxidase)–

每分子的底物被氧化需要消耗一分子氧,并且将NADPH转变成NADP+,该氧化过程消耗的氧分子中有一个氧原子出现在水中，另一个氧原子出现在产物中,故此将催化该反应的酶称为混合功能的氧化酶。5.

Modulate

Ca2+

concentrationSarcoplasmic

reticulum

肌质网:SER

instriated(横纹)muscle

cells,sequestering

(隔绝)calcium

ions

within

the

cisternal

spaceCa2+releaseCa2+

recoverMusclecontractionMusclerelaxingCa2+肌质网有关粗面内质网的发达程度可作为细胞分化程度和功能状态的一种形态特征，下面哪种说法是错误的：A．分化程度低的细胞，粗面内质网不发达B．胰腺细胞中粗面内质网发达C．胚胎细胞及干细胞中粗面内质网不发达D．浆细胞中粗面内质网发达E．生长速度快，恶性程度高的肿瘤细胞中，粗面内质网发达9.2.3粗面内质网的功能--信号肽与蛋白质膜结合核糖体

蛋白质的去向（P355）蛋白到ER

腔中的蛋白质RER中的酶类基体的酶溶酶体的酶整合膜蛋白ER膜的糖蛋白基体的膜糖蛋白溶酶体的膜糖蛋白质膜糖蛋白核膜糖蛋白质膜脂锚定蛋白（位于质膜的外侧面）质膜的外周蛋白（位于质膜的外侧面）32蛋白质进入核糖体实验信号肽的证实G.Blobel等用离体实验证实了信号肽的存在:RER对产物的影响蛋白水解酶实验多聚核糖体的离体翻译体外实验多聚核糖体实验信号序列的特性序列特征15-35个氨基酸残基，N端含有1个或多个带正电荷的氨基酸，其后含有6-12个疏水残基位置:N-端突出的一段肽内含信号肽早期信号假说(signal

hypothesis)1975年，Blobel等正式提出了信号假说,要点是:蛋白

始于游离核糖体;N端信号序列靠

碰撞与内质网膜接触,然后

内质网的膜;蛋白质以袢环形式穿过内质网的膜;蛋白的存在方式:若信号序列被信号肽酶切除:完全进入腔若是停止转移信号:膜蛋白信号识别颗粒与停靠蛋白－信号假说的补充signal

recognition

partical, SRP

信号识别蛋白SRP

is

a

cytosolic

ribonucleoprotein

particle

核糖