9: .8 .1' 3.2; also :7r7..!1', 2 t. my: - "Fete..i;~-;.:e:~t;r,~.i ;=.'%;':~..~.,~.ig;w,t.v;;..t;.:mares:-wet-0; with": 'gfsxemvrwis: -.-!..-.~if- {Ft -ogtvv'w lVi "'7 33" ""1537": ii": a?  ' mi n
fittt .hw 3? ,iqxgy ~ ttf sw *ew'wf'i...ih"t.zt Ivkgffzif " vefl-got ,ggxebg *styfawji? 5",w 353  . 1;?- itt
stag. 2..:.:2.1.;~- ;_-.;.-:i:f.i*f5-.#, f gzi;;t~s!=z.*i-3;., - .igatgugc 2,239 ~ fkgi " its? 6 attire i:-..:as'..;';s=;if,-..~:.; ,. . :ifrzwiler? . 5? ' "9*": gig t? Zegi137i3."15533??? : To
z..;.'-r.ti:-:i 35.33 may .5 .1 i... .3",er gr, . ":45.-1,.;1-;..:_;t~",;. -"_;:'1_.,Lrv*tz_..,= 325a. y";:-z.,.  .. .6323eagigw-:-%.iti,jtii? In ghetr .- " i- 5:: 5 3:53: -' -~ "2 9.22:: " " 9? .4713; at

i. .;~ ...: , e a ; g. W 75"; - ~:. ...;,-.fg._a.e.. r._-.,. y '- @143, > are ., .4. x?r_',=.,. .s--Vms  m . 7.53? 4 ' *:J-..":.. satin;- '1" *f K " " - 123 ""1"; "   ' H W" ""1! in? . at. 3:13.52 :2 E", 2 an"?

em; 3e h N W... 5. x. iiseiibigvga  ;; it 7': i = .w i g'w 1 re . a - if? i~ 5&3  .
. a y. ,, .t(. v. .- , .~ ...-.:.n. was. a. ;- $7.4": ' <1; ~tbtif.:.y; sor-3taegtg; .{If Aieiifiiifi"....j"f,=:f33." 34,... 4.* "1 17:17:17.." orel-.2;taxi-1713443.$5;2 taii35fusi  ~ 7" .-$1
. *_  '. -.. l;~,e_-,:vti'7i-; ' ' ' l V I V 37" ' ~15 2.

.-----__ . ...-<,ie.: . f : - :.:-.'".T ".xx':v'v7' 

f 2003 PROGRAM 3; 3:32, "g Twent 'Nlnth Annua| \ 53:64}? It -1
C . zeta 1%}\ _ ' .- -,~. Ju

8:30 am. Registration and Continental Breakfast fibronectin region and a putative kinase domain. The gene encod- 2 3 12,, Symposmm on .2511 {k 
Atrium (Room 1-65), William T. Young Library ing Kalirin uses multiple promoters and alternative splicing to gen- g g .3 '3 l?  3':i'.":#:.;.::t-=i: ;T.:%ii::,2f6="3 ,

erate over a dozen different combinations of functional domains. E 1 ac) - 1i ! digit-'75:. at I I I I t..;t.":..i,&

9:00 am. Welcome by Dr. Lee T. Todd, J_r., president, The spectrin-like region of Kalirin and Trio is the site of interaction 3 8 e x 2 tn : C he IStry J 1,
University of Kentucky. - Auditorium (Room 1- with peptidylglycine alpha-amidating monooxygenase (a secretory : 0'. < S E ifg" 13" #:- tfm

62), William T. Young Library granule enzyme), the inducible form of nitric acid synthase. and E (D. o. 3 a; WFIQ V & Eigfii'mf

. . huntingtin associated protein. The first GEF domain of Kalirin and q. 3 E 0- :?"?  bz' {29.33.59
9.05 am. lrftroductory Remarks - Dr. Tae H. Ji, Univer- Trio activates Raci and RhoG while the second GEF domain acti- 5 3 igbkh I if. Pyi 0
Sity of Kentucky vates RhoA. Expression of dual GEF isoforms of Kalirin causes 2 i,~%.i:, " b Mo Iecu Iar s;:

. exuberant outgrowth of axons from sympathetic neurons while I'ilr'ifw: (5 3
9.10 am. Dr. Susumu Tonegawa, Massachusetts Institute expression of a mono GEF isoform of Kalirin greatly increases the if: .5.{_ "A I ' .. [if it
t Technology ,, number of dendritic spines in hippocampal and cortical neurons. iiikggf BIOlogy ,?:f;i;{i';~; L

Memory Ftecall lmportantly, antisense-mediated reductions in Kalirin expression vm {WSyi} J;

. .. . result ins ineretract' n  " " ' k ,9 .I H

Father?) compiet'oni the ability to retrieve complete memo and Trio rzay play pivotingligsci:l:?;:acl)ifntgigmgggcaawtidoe12]:in it? Ne \ Iggy. 5:33;?

ries on t e asis o incomplete sets of cues, is a crucial function '  I. 221% 13:  m1w1sf
9f biological memory systems. The extensive recurrent connec- of extracellular signals and the actin cytoskeleton. :1 \ \ w:
tiVity of the QAS area of hippocampus has led to suggestions that 1:50 pm. Break 2 'fitji'f" *7 hay?

it might prowde this function. We have tested this hypothesis by E; :3? it, I. $4.4"
generating and analyzing a genetically engineered mouse strain 2-00 p m Dr Ashley I Bush Massach MSW: A ti;giw?

. . . . . . . usetts General in... "i" " " 7"

In which the Nmethyl-D-asparate (NMDA) receptor gene is ab- Hospital and Harvard Medical School "IE? / \ $91?
lated specifically in the CA3. Pyramidal cells of adult mice. The Metal Ions, ,B-Amyloids and Alzheimer's Disease ii? 55in LEV-'2 I \ \  :l' :5;
mutant mice normally acquired and retrieved spatial reference , 7:35inf-3.:Qf. 1:33;: (:3: 1
memory I} the Morris water maze. but they were impaired in re- , AB is the principal component of the plaque pathology which 3313:3354 2"?! g???" 5
trievmg ihl? memQVY When presented with a fraction of the original Is the hallmark of Alzheimers disease (AD). We have characterized my a. '  fix it? W3 l
0995. Similarly, hippocampal CA1 pyramidal cells in mutant mice AB asauQ'qutOUS metalloprotein, With selective high-affinity binding $3? if eStabllShed m the memory Of pr,
displayed normal plaCe-related activity in a full-cue environment Sites. for Z'nC (K5!z 100 nM) and copper (K31z 10 attoM). Several angst; T3; Anna 8 Na 597? Eigdi i
but showed a reduction in activity upon partial cue removal. These studies have reported that there is an elevation 0f zinc and copper I 353;;33e5i3" i I high 34 1
result? Provide direct evidence for CA3 NMDA receptor involve- in the plaques in Alzheimers disease. Furthermore, genetic ablation i I I {1332 ----- {'in 33
merit m assomative memory recall. of the ZnT3 transporter, which loads zinc into the glutamatergic lt?:{s- Skiff; t}

. SYnapse, abolishes amyloid de osition in the T 2576 mouse mod I a. ~ 1' ' 1)

10:00 am. Poster Sessmn, Room 137, Chemistry-Physics for AD. p g e .o x  NeurOSCIence Wag
Building :43 binds Cu and Zn through a site that involves oligomeric Lo Hf: 5:}

Pepti e assembly. and resembles the structure of SOD1. When Lo r  N

11 :45 a.m. Buffet Lunch, Faculty Club [Please return regis- synthetic AB binds copper in the absence of zinc, it is highly redox v? 8 3%15 '65  '2; Fl-f .1".
tration card by April 11, 2003 for reservations] active. Biolo ical reducin a ents such as do a ' ,9 > ' 1'5: $53.9} {if L, ">::;ji$m

' I g g g p mine, cholesterol x <.0 1hr. Vi SPEAKERS ',v. e m..-_. r: A.

. _ . _ . and Vitamin C can act as a reservoir of electron donation, so that E O 0 g 2} FIE; .~'T~:=7..'E-fii
1.00 pm. 3r. littllfleardtMains, University of Connecticut the AB/Cu complex acts as a catalyst generating H202 (Km: 5 pM g 3 8 1H t.:z?g~,
ea en er Vmax: 3O nM/min) The toxicity of AB species is pro ' , C ttux I tisif'iiret-L:

n . . , ,. . , - portional to O V  "m" ' at: H

Kalirin and Trio. A Medley of lnteractors the peptides ability to reduce Cu or Fe and generate H20 (AB42> M E >_ 17:.- ,3 Susumu Toneggwa *3 rft

. . . .. AB4O >rat AB). / 2 0 ._ x 4 31314 Richard E. Mains 31"

PreCise control of the actin cytoskeleton is critical to many Chelators of copper and zinc both disa K t A  E o Iw )&M
cellular functions; members of the Rho subfamily of small GTP from post-modem human brain and al i biaa: p13 dipt3t8* CD 3 If git/3353:) AShIey l' BUSh Qaki";
bindin rowing Ia esse . . . . : n. _ "re? ti. .T; .;.
GTPagepactivatirFiJQ actorsnt(|g|Agl:)s ggRs/CgToFfejihrnzgdflggpotr: Vile haveirecengygndhtgat one such bioae c elator. E 9 g; le {1in

. ,. . , , 0 io UinO, mar e in - - . . . . a) 15" ,2? .gws : 3. ""5-'.= 'il

(GEFs) of the Dbl family are critical to the activation of the large mic: This corn 0y d -| 8 brain am y\K-j path ogy In 92576 8 2 E Mi?" 533*; F Id A II 18 2 Q
family of Rho proteins. While most Rho GEFs have a single Dbl com .leted a Phapseu; clilns' alrtetir|ed Elngbioticlegd h recently a) C is hit? 5'?an I'I av, p" 5 003 43"}:
homology (DH) domain, Kalirin and Trio define a small family of P ica net in z ei e. D D _l iiak" Jami
structurally related dual GEF proteins facilitating the coordinate 3-00 ' ' \ ' 35? Si; Riff- 5 W.

. . . 1 . pm. Reception and Meet With 8 akers Atrium " 9 M -  *5 4:31.43:
regulation of multiple Rho family members. In addition to their (Room 1-65), William T. Youpn Library :Iggji Department Of ChemlStry iyf:
two DH domainsaboth have a Sec14p domain. 9 spectrin-Iike re-  Vii??? University Of KentUCk :fm;
peats, 2 pleckstrin homology domains, 2 8H3 domainS. an IQ- (http://www.chem.uky.edu/seminarsln f elcome html) :6; I y 2"?
WEI? _ : : . . _ ,2; Lexmgton, KY 40506-0055 if?
.z' MMJJE? "'iiltt."e.,i*imgh., get-.3aurora-.2; 51:. .e , A39. 9:. , u. .., . .* ' .. .. . ' " " " ' :   at)   I M 36}..
a; .392 a: tit-y'V-fgwf ,,_..-., .E-Siguz .. 7-73,, 32"? 431,45.Egg-:42, 5;.g-.:-=:<"vl."' 5.; . .f-vre' 25$ ; 2 55.3.. gaffalgyt. f__;v:_gi,.,i;; .' W" ;, c, - :A y...,l;{,:.,~ifx-l-.";.rjgi;i.1":1.15.:,jehf'g.,..~,jl_..4_ty_;:;-jgl':;-,.y.::;:us:_';.v;; .453: ;._~:5_ ,5. ' 33 .. 53: 43.5 =:.'-' 3:9,, . emphatic" '3.

. . are . t.  m,' .:_l, -. L... T-f . f : nix-J: " __-i._. .1. 1:. ' .,-;' f: i .2 .g.'< g. l 53 ',..~ 2; .lgyfi _, 11; , "- ._ 9! - "G 59, . :3 3 >~-.\.;.~.v '5 . as? v': 333' .- ,a 'I' RH ; (1.1.,1- w' " 9 ~ -,.  '3. v " 1 "3'7 h 9" 7 "  " 3 V,   I" " 3 ~; 1 1 {2}; 4
~ e53 wage. 333?,gy .5: goose: : timed? it}; v 5': 3 '- 3W  {5 .1. 415"? egg g1 ""Mgg
u.*-eb . Y5f 13. s 9 we 26 rt ,. 1 ,JP'FS. ;~ - .9:  9' i 5 w 3
at? s/Eyiatx aevawgeigwt lttvgwig my)&,xme.% beg; tenet... wim 3?
weerts: w . .1. a conga? . eerie ,-; =.:v i... 3.. 41}3O~" e " A..$q t iii
I! I: _ I. '1 marijgudiu.1139... "W- hat: all L5.  if?! _.: _ ',. . , . t; 3... ,1 .1, .313... r . h pit-5: .7?- (52. H, . my. Ayah): ,iati,t:.x.:.:,:, .31. t, type}... ."'...:~ gauge.- - .:..- "r 5.3.}: 5 : T (13... 3... a... ,. 'tg-sfglznh '- . 3-3-51 .3335. re4i 39'! ,1 53.; ff"; 0.. 432.535-
. . .,  - ,, I :w M~9s3 t0. 3" gfift'urk' ti trig?"itq1h;vl3e*%ig