Intertwined Thiab Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, Thiab Kab Mob Part 4

3. ER Dynamics

ER tsis yog tsuas yog nyuaj hauv nws lub koom haum tab sis kuj nyob rau hauv nws cov lus tsa suab. Kev nce qib hauv kev nkag siab ntawm ER dynamics tau qeeb dua li ER morphology li cov tubules tom qab ntawd thiab cov lus tsa suab tsis tu ncua thiab kev hloov kho ntawm lub network ua rau ER nyuaj rau cov duab.

Lub endoplasmic reticulum yog ib qho ntawm cov kabmob tseem ceeb hauv cov hlwb thiab muaj ntau yam tseem ceeb hauv kev ua haujlwm lom neeg, xws li protein synthesis, glycosylation cov tshuaj tiv thaiv, lipid synthesis thiab decomposition, ion thauj thiab khaws cia, thiab lwm yam. Tsis tas li ntawd, kev tshawb fawb qhia tau hais tias tseem muaj kev sib raug zoo. nruab nrab ntawm endoplasmic reticulum thiab nco.

Ua ntej, endoplasmic reticulum ua lub luag haujlwm tseem ceeb hauv kev tswj hwm lub cev lub cev ntawm cov neurons. Ntau cov kev tshawb fawb tau pom tias endoplasmic reticulum tsis ua haujlwm tuaj yeem ua rau muaj kev cuam tshuam hauv kev loj hlob thiab kev loj hlob ntawm cov neurons, yog li cuam tshuam rau tib neeg txoj kev kawm thiab kev nco muaj peev xwm. Nyob rau tib lub sijhawm, endoplasmic reticulum tseem koom nrog hauv synaptic plasticity ntawm neurons. Los ntawm cov kev cai ntawm kev thauj mus los thiab calcium ion tso tawm, nws koom nrog hauv kev tsim thiab kev kho ntawm synaptic plasticity xws li potentiation mus ntev thiab kev nyuaj siab ntev.

Qhov thib ob, kev tshawb fawb qhia tau hais tias endoplasmic reticulum muaj kev ua haujlwm ntawm kev tswj cov neurotransmission. Lub endoplasmic reticulum ncaj qha los yog tsis ncaj qha cuam tshuam kev sib txuas lus ntawm neurons los ntawm kev tswj cov synthesis thiab thauj ntawm neurotransmitters. Yog li ntawd, kev ua haujlwm tsis zoo ntawm endoplasmic reticulum tuaj yeem ua rau muaj kev cuam tshuam loj heev ntawm cov neurotransmitter tsis txaus, ua rau muaj qhov tshwm sim tsis zoo xws li kev nco thiab kev puas hlwb.

Thaum kawg, endoplasmic reticulum kuj tseem tuaj yeem tsim thiab khaws cov lipids ntau, suav nrog sphingomyelin, uas yuav tsum tau los ntawm cov neurons. Sphingomyelin yog ib qho tseem ceeb heev rau kev tswj kev ruaj ntseg thiab kev ua haujlwm ntawm cov neurons. Yog li, lub peev xwm ntawm endoplasmic reticulum los tswj sphingomyelin ncaj qha cuam tshuam rau kev ua haujlwm ntawm lub hlwb thiab tib neeg lub cim xeeb.

Piv txwv li, kev sib raug zoo ntawm endoplasmic reticulum thiab nco yog inseparable. Los ntawm kev ntxiv dag zog rau kev nkag siab thiab kev tswj hwm ntawm endoplasmic reticulum muaj nuj nqi, peb tuaj yeem tiv thaiv thiab txhim kho tib neeg lub cim xeeb, yog li txhim kho lub neej thiab kev kawm zoo. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.

Nyem Paub Short-term Nco yuav ua li cas txhim kho

ER dynamics nyob rau hauv mammalian hlwb yuav categorized rau peb hom: oscillation ntawm tsim network ntsiab; cov dynamics ntawm hais nyob rau hauv lub ER lumen los yog daim nyias nyias; thiab tiam ntawm cov ntsiab lus network tshiab (saib daim duab 3).

Lub hom phiaj ntawm ER dynamics tseem tsis tau paub meej, tab sis qhov tseem ceeb tshaj plaws txoj kev xav yog tias oscillationsaccelerate cov txheej txheem ua nyob rau hauv ER los ntawm kev pab txhawb kev txav ntawm lumenal thiab transmembrane hais [25,180,181].

3.1. Cytoskeletal Control ntawm ER Dynamics

ER tas li rov kho nws lub koom haum spatial. Lub zog zoo ntawm ER tau pom nyob rau hauv cov kab lis kev cai CV1 hlwb [182], cov qog hlwb tshiab [23], thiab cov kab mob loj hlob hauv kab lis kev cai neurons [183] ​​ntev ua ntej kev tshawb pom ntawm ntsuab fluorescent protein (GFP), los ntawm kev siv cov lipophilic dye DiOC 6.

Cov tubules tshiab tuaj yeem raug rub tawm los ntawm lub network uas twb muaj lawm thiab fused mus rau cov tubules nyob sib ze lossis cov junctions los tsim kev sib txuas tshiab, thiab cov polygons network tuaj yeem tsim thiab ploj mus ([182]; Daim duab 4). Qhov kev txav ntawm microtubule-motor-driven no tau piav qhia hauv Tshooj 3.1.1. Qhov kev faib ua feem ntawm lub network hauv nplooj ntawv thiab tubules kuj tuaj yeem hloov pauv dynamically.

ER nplooj ntawv rov ua dua rau hauv tubules thaum ribosomes raug stripped los ntawm lawv qhov chaw nrog puromycin [45]. Raws li tau piav qhia hauv qab no, inhibitingmicrotubule-raws li tubule txav tuaj yeem ua rau nce qhov feem ntawm daim ntawv-likeregions. Kev nkag mus rau hauv mitosis tau raug tshaj tawm los ua rau cov ntawv nthuav dav [37,43,184], txawm hais tias lwm cov kev tshawb fawb tau pom tias muaj kev txhim kho mitotic tubulation [45] uas tau tsav los ntawm REPs 3 thiab 4 [185].

Qhov kev hloov pauv zoo li no tuaj yeem pab cov organelle coj mus kuaj lub cellular ntim sai sai [1] thiab teb rau cov kev hloov pauv ntawm cov cellular xav tau thiab noj zaub mov zoo (Ntu 3.1.3).

ER-koom nrog microtubule motors tsis yog tib txoj kev uas ER cuam tshuam nrog cytoskeleton, thiab hauv cov ntu hauv qab no, peb piav qhia txog yuav ua li castubules tuaj yeem txuas ntxiv los ntawm kev cuam tshuam nrog cov microtubules loj hlob ntawm cov lus txuas txuas (TACs) thiab los ntawm kev koom tes nrog motile MCSs.

Kev sib cuam tshuam zoo li qub ntawm ER tubules nrog microtubules thiab lub luag haujlwm ua los ntawm actin cytoskeleton kuj tau piav qhia.

3.1.1. Microtubule Motors Tsav ER Dynamics

Cov kev tshawb fawb thaum ntxov siv DiOC6 qhia tias ER tubules nyob rau hauv lub cell periphery feem ntau coaligned ze nrog microtubules [23,183,186], raws li tau lees paub nyob rau hauv ntau cov kev tshawb fawb tom qab (xws li, [21,38,187]).

Lub nplhaib rearrangement thiab tubule branching kuj tshwm sim nyob rau hauv koom nrog microtubules [38]. Lub depolymerization ntawm microtubules kiag li inhibited ER tubule thiab network dynamics nyob rau hauv VERO hlwb [20] nce tus nqi ntawm ER nyob rau hauv daim ntawv-likestructures thiab txo cov tubular network [20,37,38,186,188].

Super-resolution imagingin nyob hlwb tau pom tias cov nplooj ntawv no muaj kev sib xyaw ntawm morphologies, nrog rau cov nplooj ntawv tuab, cov ntawv nyias nyias uas muaj cov nanoholes, thiab cov tubular network ntom ntom [33], qhia tias microtubules tsis tsuas yog tswj txoj haujlwm ntawm ER network tab sis kuj tseem txhawb nqa. cov ncauj lus kom ntxaws lub koom haum ntawm ER membrane domains.

Kev pom ncaj qha ntawm ER-zoo li tubules txuas nrog microtubules tau ua ntej los ntawm kev tshuaj xyuas hauv vitro siv cov khoom rho tawm los ntawm CV1 hlwb [189] lossis interphase Xenopus qe [190] qhov twg video-txhim kho qhov sib txawv cuam tshuam qhov sib txawv microscopy qhia cov membrane tubulessliding raws microtubules. Xenopus tes hauj lwm tau pom tias yog ER los ntawm antibodylabeling thiab muaj cov polysomes ntawm daim nyias nyias [19].

Motility coj tubules nyob rau hauv kev sib cuag nrog ib leeg, ua rau tubule fusion [19,20,189] uas yog atlasstin-dependent [184]. Tsis tas li ntawd, ob qho tib si du thiab ntxhib ER los ntawm nas daim siab tsim motilenetworks thaum ua ke nrog interphase Xenopus qe cytosol, ua qauv qhia txog kev txuag ntawm motility thiab membrane fusion [191]. Txawm li cas los xij, yog tias qhov concentration ntawm daim nyias nyias yog siab txaus hauv vitro, ER tubule network tuaj yeem tsim nyob rau hauv qhov tsis muaj microtubules [192].

Lub cev muaj zog zawv zawg ntawm ER tubules raws microtubules txij li tau pom ntau zaus siv fluorescence microscopy (piv txwv li, [20–22,38]).Vim microtubules tau taw qhia nyob rau hauv feem ntau cov kab mob uas tsis yog-neuronal hlwb nrog lawv cov dynamic 'plus' xaus ntawm lub cell periphery, nrawm sab nraud ER tubule zawv zawg yuav tsum aplus-kawg-qhia microtubule lub cev muaj zog. Tus tsim tswv cuab ntawm kinesin superfamily, kinesin-1, yog lub luag haujlwm rau qhov kev txav no [20,193,194].

Inhibition ntawm kinesin -1 tsis tsuas yog inhibited sab nraud tubule txav tab sis kuj nce qhov feem ntawm ER daim ntawv cheeb tsam nyob rau hauv lub cell periphery [20]. Muab hais tias daim ntawv zoo li cov cheeb tsam tuaj yeem muaj xws li cov khoom sib txuas ntawm cov tubular sib txuas [34] lossis cov nplooj ntawv uas muaj nanoholes [33], nws yuav nthuav tawm yog tias cov nplooj ntawv no sib haum nrog ob hom qauv, lossis yog tias muaj kev sib xyaw ntawm morphologies, raws li pom tom qab. Kev kho mob ntawm nocodazole [33]

Feem ntau kinesin -1 hauv cov tsiaj hlwb istetrameric, suav nrog ob lub cev muaj zog zoo tib yam (KIF5) subunits thiab ob lub KLCs zoo tib yam [195].Vertebrates nthuav qhia peb KIF5 noob: KIF5B tau nthuav tawm thoob plaws, thaum KIF5A thiabC yog cov khoom noj muaj txiaj ntsig zoo. Peb yuav rov qab mus rau KIF5A tom qab txij li kev hloov pauv ua rau cov kab mob neurodegenerative (Table 1) [195]. Muaj plaub KLC noob, nrog KLCs 1, 2, thiab 4 tau nthuav dav.

KLC1 ​​muaj nyob rau hauv ntau daim ntawv hloov pauv, nrog rau KLC1B yuav tsum tau ua rau ER motility [20,193].Qhov lus nug tseem ceeb yog tus kheej ntawm kinesin-1 receptor hauv ER. Ntau tus neeg sib tw tau thov, tab sis muaj lus ceeb toom nrog txhua tus. ntawm lawv. Tej zaum yuav muaj cov receptors sib txawv hauv cov neuronal vs. non-neuronal hlwb, thiab nyob rau hauv cov ntaub so ntswg sib txawv.Kinectin tau txheeb xyuas siv cov tshuaj tiv thaiv kab mob monoclonal [196] thiab khi rau KIF5 C-terminus [197].

Kinectin tau cuam tshuam nrog kev tswj hwm ntawm focaladhesion dynamics thaum lub sij hawm chemotaxis los ntawm kev txhawb ER lub hom phiaj rau focal adhesions ntawm lub xov tooj ntawm cov thawj ntug [198,199].

Interestingly, Rab18 yuav tsum tau rau cov txheej txheem no thiab formsa ternary complex nrog kinectin thiab kinesin -1 [198]. Txawm li cas los xij, kinectin knock-out micehad tsis muaj phenotype, nrog rau ib txwm ER (thiab lwm yam organelle) faib hauv KO MEFs [200].

Tsis tas li ntawd, nyob rau hauv kab lis kev cai neurons, ER txuas mus rau tag nrho cov axons, tsis tau kinectin tsuas yog pom nyob rau hauv lub cev ntawm tes [194], ua raws li nws lub luag haujlwm hauv kev tswj hwm ERsheet spacing [13].

Txawm li cas los xij, siRNA depletion ntawm kinectin txo ER networkdynamics hauv Cos-7 hlwb [26]. Intriguingly, Rab10 tseem cuam tshuam rau kev tswj hwm ERtubule tsim [7] thiab tau tshaj tawm los ua ib qho nyuaj nrog JIP1, ib qho neuronallyexpressed kinesin adaptor, thiab KLC1, los txhawb kev thauj cov secretory vesicles thaum lub sij hawm neuronal polarization thiab axon kev loj hlob [201].

Txawm hais tias qhov complex no koom nrog hauv ERtubule txuas ntxiv hauv cov neurons, thiab seb Rab18-kinectin-KIF5B complex puas xav tau rau ER tubule txuas ntxiv hauv cov hlwb uas tsis yog tsiv teb tsaws yog qhib cov lus nug.Lwm tus neeg sib tw ER kinesin-1 receptor yog p180 , uas sib koom homology nrog kinectin'skinesin-1 binding domain [202], thiab uas, zoo li kinectin, kuj tau nyob hauv thaj chaw hauv nruab nrab ntawm cov ntawv hauv cov hlwb uas tsis yog neuronal [13,16,194].

 Hauv kab lis kev cai neurons, txawm li cas los xij, p180 hauv cheeb tsam tsis yog rau cov nplooj ntawv hauv lub cev ntawm tes, tab sis kuj rau tubules hauv axons, tab sis tsis yog dendrites [194], alocalization zoo ib yam nrog KIF5 khi. Txawm li cas los xij, nws yuav ua tau raws li kev thauj mus los ntawm ER thiab microtubules es tsis yog kinesin -1 receptor (saib Tshooj 3.1.3).Muaj ob tus neeg sib tw kinesin receptors ntxiv.

Protrudin (gene lub npe ZFYVE27) yog ER-neeg nyob hauv kinesin khi cov protein nrog lub luag haujlwm tseem ceeb hauv kev tsim cov motile lateendosome-ER MCS motility, raws li tau piav qhia hauv Tshooj 3.1.2. Txawm li cas los xij, nws tau hais tawm tsawg kawg nkaus (tsis pom nyob rau hauv HeLa cell proteome [203]), thiab thaum nws depletion withsiRNA ua rau lig endosome pawg ntawm lub cell center [204,205], nws tsis paub meej tias qhov no cuam tshuam li cas ntawm ER faib.

Thaum kawg, ER-localised transmembrane DNA-J-domainprotein B14 tau pom tias muaj kev cuam tshuam nrog KIF5B los tsim ib qho chaw rau SV40 tus kab mob tso tawm ntawm ER [206], tab sis nws txoj kev koom tes hauv ER dynamics ib txwm tseem yuav tau sim.

Muab hais tias ER txuas mus rau sab nraud los ntawm lub hnab ntawv nuclear ntawm lub cellperiphery, qhov kev xav tsis tau pom yog tias ER tubules txav mus rau microtubule minusends hauv interphase Xenopus qe rho tawm, tsav los ntawm dynein [19,184,190,207,208].

Qhov no haum nrog qhov yuav tsum tau muaj rau dynein ntawm lub hnab ntawv nuclear los tsav cov neeg tsiv teb tsaws chaw pronuclear, uas tuaj yeem rov tsim dua hauv cov kev rho tawm no [209]. Txawm li cas los xij, tshwj xeeb tshaj yog dynein-drivenER motility txuas ntxiv txawm tias nyob rau hauv cov khoom rho tawm los ntawm embryos tom qab kev faib tawm thib tsib: kinesin-dependent ER txav tsuas yog pom thaum cytosol los ntawm tadpole cell kab raug siv [187].

Kev ua haujlwm tsis ntev los no tau muab cov lus piav qhia txaus siab rau qhov tshwm sim no [210]: lub pas dej perinuclear ntawm ER uas tsim los ntawm kev ua haujlwm dynein yog xav tau los sib sau cov nuclei loj pom nyob rau hauv cov embryos thaum ntxov (sea urchin thiab Xenopus embryos hauv txoj kev tshawb no).

Tsis tas li ntawd, nthuav qhia ntxiv reticulon 4b txo qhov loj ntawm nuclei, xav tias yuav txo tau qhov tsim ntawm ER daim ntawv cheeb tsam [210]. Xenopus qe rho tawm kuj tau nthuav tawm lub voj voog ntawm lub voj voog-raws li kev hloov pauv hauv ER dynamics, nrog dynein-tsav txav txav tau inhibited hauv metaphase-nrhiav rho tawm [184,190,207] thaum myosin V-driven ERmotility ntawm actin filaments tau qhib [211].

ER nplooj ntawv sau tau [184], raws li tau tshaj tawm hauv mitotic HeLa hlwb [37], txawm hais tias lwm cov kev tshawb fawb tsis sib haum rau qhov no [45,185] .Dynein tsis yog ib qho tseem ceeb ER lub cev muaj zog hauv embryonic hlwb. Nyob ib ncig ntawm ib nrab ntawm nrawm dua tubule txav hauv VERO hlwb tau tshwm sim ntawm qhov chaw ntawm tes thiab tau tsav dynein-tsav [20].

Tsis tas li ntawd, qhov inhibition ntawm dynein ua rau muaj qhov sib txuam ntawm ERsheets hauv lub cell periphery yam tsis muaj kev cuam tshuam rau sab nraud, kinesin-tsav txav [20].Ib yam li ntawd, ob qho tib si dynein thiab kinesin-1 tsav ER tubule motility hauv axons [194] thiab dendrites [212,213] ntawm kab lis kev cai nas hippocampal neurons. Raws li tsis tau, tus receptor rau dyneinon ER tsis tau txheeb xyuas nyob rau hauv ib qho system, tsis zoo li rau ERES (Section 2.2.2).

Ib qho piv txwv kawg ntawm microtubule-lub cev muaj zog-tsav txav uas cuam tshuam nrog ER yog muab los ntawm kev tsiv teb tsaws chaw thiab qhov chaw. Raws li cov pro-nuclear tsiv teb tsaws tau hais los saum toj no, kinesin thiab dynein koom tes ua haujlwm nuclear nyob rau hauv ntau yam sib txawv, xws li thaum lub sij hawm neuronal nuclear migration thaum lub hlwb loj hlob [214] thiab nuclear txav ntawm ntau theem ntawm C. elegans txoj kev loj hlob [215].

Dynein ntawm lub hnab ntawv nuclear yog ib qho tseem ceeb rau kev sib cais centrosome nyob rau hauv lig G2 / prophase thiab pab txhawb kev tawg ntawm nuclearenvelope (saib hauv [216]). Kinesin-1 kuj koom nrog hauv centrosome thiab nuclear positioning nyob rau hauv cov hlwb uas tsis yog-polarised, qhov uas nws yog recruited rau lub nuclear envelopeby RanBP2 thiab BICD2 [217].

Interestingly, nesprin 4 yog qhia tshwj xeeb ntawm lub hnab ntawv sab nraud hauv polarized epithelia, qhov uas nws recruits kinesin-1 uas ces translocates lub nucleus mus rau hauv paus ntawm lub cell [218].

For more information:1950477648nn@gmail.com