???? ???? ?????? ?? ???? ?????

1
???? 4 ???????? ?????? ?????? ???????
2
???????? ?????? ?????? ???????
3
???????? ?????? ?????? ???????
4
???????? ?????? ?????? ???????
???? ???? ?????? ?? ???? ????? ?????? ???
???? ???? ???? ??? ???????, ??????? ????
????? ??????? ?? ??????? (????? ???????)
5
????? ????? ??????? ??? ???? ?? ???????? ???????
????? ???? ?????
????????
??????????? ?? ??? ??? ????? ?????? ????
?????????? ?? ???????? ????? (????? ????? ??? ???)
6
non-epithelial cells
epithelial cells
tight junctions
actin
adhesion belt (CADHERINS)
CELL - CELL ADHESION
CADHERINS IG-LIKE CAMS INTEGRINS SELECTINS
desmosomes (CADHERINS)
Gap junctions (connexins)
focal contacts (integrins)
hemidesm. (integrins)
CELL - MATRIX ADHESION
integrins
NO attachment plague
basal lamina
Non-JUNCTIONAL CONTACTS
JUNCTIONAL ADHESION MECHANISMS
7
???????? ?????? ?????, ???????? ????? ?????
"???? ???" ?????? ????? ???? ????? ?????
??????? ????? ???????? ??????? ???????
??????? ????? ??????? ??? ????? ?????? ?? ???
Chemo-attraction Chemo-repulsion
8
???????? ????????? ??????
Ig superfamily Cadherins Integrins Netrins Semaph
orines Laminims Collagen Tenascins Receptor
tyrosin phosphatase kinase
9
CELL-CELL adhesion
CELL ADHESION MOLECULES
Cadh. repeats
Cadherins Ca 2 -dep. homophilic adhesion
functional unit dimer Immunoglobin
superfamily (CAMs) homophilic or
heterophilic Selectins heterophilic P selectin
counter-receptor PSGL-1,
glycosylated Integrins heterodimers,
heterophilic bind to ECM, Ig-CAMs,
cadherins adhesion, polarity, migration
Ig and Fn III repeats
lectin repeats
I-CAM
Hynes TiCB 9M33 1999
10
??????? ?????? ??????? ?????? ?? ????????
??????? ???????? ?????? ???????? ??????? ????
??? ???????? ?? ??? ???? ?????
???? ??????
11
?????? ?????? ??? ???? ?? ??? Cell-Cell adhesion
molecules
??? ????? ??????? ???? ???? ?????? ???? ?????
??????? ????? ?????? ????? ???????? ????? ????
?????? ?????
12
Some adhesion molecules involved in axon
growth Cell adhesion molecules (CAMs) Name
Similar/identical molecules Comments N-cadhe
rin (mouse) N-CalCAM (chick) Calcium-dependent
A-CAM (chick) NCAM BSP-2 Immunoglobulin
superfamily LI (mouse) NILE (rat)
Immunoglobulin G4, Ng-CAM, 809 (chick)
superfamily Nr-CAM, neurofascin Neuroglian
(insects) TAG-1 (rat) Axonin-1, F11
Immunoglobulin superfamily Fasciclins
Insects.Fasciclin II is the
orthologue
13
Some adhesion molecules involved in axon
growth Substrate adhesion molecules (SAMs) Name
Similar/identical molecules Comments laminin
Binds to Integrin Fibronectin Binds to
Integrin Tenascin Cytotactin,J1, myotendinou
s antigen Collagen
14
Cadherin Ca dependent cell cell adhesion
????? ????? ????? ??? ???? ???????
??? ??????????? 700-750 ?.? 5 extracellular
domains (100 a.acid) ?????? ?????? ???? ????
????? ????? ???? ????? ????? ???? ???? ????
????? ????? ?????? via Catenins ?????
???????? ?? ????????
15
??????? ??????? ????? ??? ???????? ???? ??????
16
????? ???????? ????? ????? ??? CATHENIN ? ?(????
????? ?? ?? ???????? ?????) ???? ?? CATHENIN
????? ??????? ?? ???????? ????? ??? ?? ??????
????? ???? ?????????? ?????? ??? ???? ???????????
?? Lymphoid enhancer factor 1
17
CAM- Cell Adhesion Molecule In neurons N-CAM
???? ? Ig superfamily (At least one Ig-like
domain with type II fibronectin domain) Known
20 different types Formed by alternative
splicing
Ca independent
????????? ???? ???? ???? ??????????? ????
???????? ????? ?? ???? ??????? ????
???? ????? ????????
18
NCAM- PSA Post translation modification by
sialic acid
Sialic acid ???? ???? ????? ????? ? IG-DOMAIN
?????? ?? ??? ?????? PST-1 ??? ??????? ?? ????
???? ??? ????? ????? ??????? ????? ??????
PSA ???? ????? ???? ??????? ?? ????? (????
???\???) NCAM ??????? PSA ????? ?????????? ???
PSA ????? ?????????? ?????? PSA ???? ???
????? ??? ????????? TRK ? FGF.
19
N-CAM in neurogenesis and synaptic plasticity
20
???? ????? SA ???????? NCAM ?????? ??
??????? ????? ?? ????? ??????? LTP ??? ??????
??? ????????, ?????, ???????.
??? NCAM-PSA ????? ????? ???????? ????? ???
????? ????? ?? ??????? ???????? ??????? ??
??????.
21
PSA-NCAM - red
PSA-NCAM
PSA-NCAM
BrdU
PSA-NCAM in the subventricular zone (SVZ) and
olfactory bulb of the adult rat
22
PSA-NCAM in the cerebellum of peri-puberal rabbit
23
????????? ?? NCAM ????? ????????
??????????? ?????? ????? ??????? NCAM ?????
???????? ??????? (???? ???? ????? ????? ?????)
???????? ?????????? Fasciclin II (?????? ???
????) ???? ???? ?????? ??????? - ?? ?????
???????? ??? ???? ???????
24
Fascilin II
???? ??????? ???? ????? ?????? ???? T-BAR ???
??????
25
Fas II mechanism of action
K channel mutant (EAG)
cAMP mutant (dunce)
26
??????? ????? ? INPUT ??? ???????????.
27
?????? ?????? ?? ??????? ?? ???? CAMS NCAM,
L1, Cadherin Axonin-1, Ng-CAM, Nr-CAM
Cadherin - ????? ?????? ???, ????? ??????? ????
?????? NCAM ? IG ????? ?????? ????? ?? ????
??? ?????, ??????? ???? ????? ??????
28
Intra cellular
vinculin
talin
a-actinin
signalling molecules
laminin
fibronectin
Integrin a5b1 fibronectin receptor Integrin
a6b1 laminin receptor
29
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30
Neuroligin-1
PDZ binding domain
31
Neuroligin-1
Neurologin interacts mainly with the 3rd PDZ
domain in the PSD95
Interact also with SAP102, PSD-93, S-SCAM,
Magi 1 and 3, Shank 1 and 3, Pick 1, GOPC,
SPAR,
PSD95- 3 PDZ domains, SH3 domain, guanilate
kinase domain
32
Neurexin/s
Neurologin binding to its receptors a or b
neurexin depends on alternative splicing of
neuroligin.
33
Neuroligin/Neurexin clustering in the synapse
Involvement in development Neurologin 1-
Expression increased postnatally
(P1-P8) Neurexin expression from E10
34
Neuroligin/Neurexin and synaptic strength
35
Intra cellular
vinculin
talin
a-actinin
signalling molecules
laminin
fibronectin
Integrin a5b1 fibronectin receptor Integrin
a6b1 laminin receptor
36
Sakisaka, T. et al. J Cell Sci 20051185407-5410
37
(No Transcript)
38
(No Transcript)
39
Cell adhesion molecules involved in axonal
guidance and path finding
Robo - slit
Fas II
40
Eph and Eph receptor