Cargos and Genes

7/23/2019 Cargos and Genes

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Cargos and Genes: Insights into

Vesicular Transport from

Inherited Human Disease

BIOLOGY 150 G

San Agustin, Ma. Katreena

Frances Sison, Sanden Aejas

Santos, Kristine Marie

Solis, A! Gail

"aro#a, $eil


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INTRODUCTION

%esicular "rans&ort

' #ajor &at()a!s*

a+ Secretor!

+ $onsecretor!


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INTRODUCTION

In(erited disorders o- trac/ing I"+

a+ isorders o- cargo recruit#ent and2esicle iogenesis

+ e-ects in 3a and ot(er G"4asesand associated &roteins

c+ Anor#alities in t(e c!tos/eleton andc!tos/eletonassociated &roteins

d+ e-ects in 2esicular tet(ering and

-usion


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Defects in Rab roteins and in

Vesicular Tethering and !usion


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R"# ROT$IN%Rab 27A and Rab 3A


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Rab roteins


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Rab&'"

3a -a#il!

Secretor! cells Melanoso#e trans&ort

Mutation in 3a'A

istur #o2e#ent o- #elanoso#e

istur targeting o- secretor!l!soso#es o- c!toto6ic "cells


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Griscelli %(ndrome

7!&o&ig#entation o- s/in

Sil2er! gra! (air

Accu#ulation o- endstage#elanoso#e


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$ffects of G%

ela!ed de2eloent

Intellectual disailit!

Sei8ures 7!&otonia

9!e and 2ision anor#alities

4rone to recurrent in-ections 7e#o&(agoc!tic l!#&(o(istioc!tosis7L7+

a#ages organs and tissues


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Rab )"

Most aundantl! e6&ressed 3a &roteinin t(e rain

7ig( e6&ression in &ancreatic islet cells

negati2e role in insulin secretion Mutations in t)o genes -or 3a:Aregulation causes neurode2eloentalde-ects*

a+ Mutation in gene encoding -or 3aGI;


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*+% and +artsolf %(ndrome

=MS

>atal!tic suunit o- 3a:GA4

e2eloental de-ects o- t(e e!e#icrocornea, cataract, o&tic atro&(!+and rain #icroce&(al!, #entalretardation+, and #icrogenitalia

Martsol- S!ndro#e

$oncatal!tic suunit o- 3a:GA4

Si#ilar )it( =MS ut #ilder &(enot!&e


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*arburg +icro %(ndrome,*+%-


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*arburg +icro %(ndrome

Mutation in 3a:GA4 gene t(atencodes -or 3AB: G"4ase >on2erts acti2e 3a:G"4 to inacti2e

3a:G4

Accu#ulation o- G"4ound -or# o-3a:A In(iition o- >a'? de&endentgluata#ate release -ro# cererocortical

s!na&otoso#es. Anor#alit! in e6oc!tosis ecause o-

su&&ressed dissociation o- 3a:a -ro#s!na&tic 2esicles

$o s&eci@c treat#ent


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C$DNI. %/NDRO+$Mutation in SNAP 29


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Cause of C$DNI. %(ndrome

Insertion atc$A

&ositionC

Loss o-S$A4 'D

Anor#alit! in

%esicular"rans&ort


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%N" &0 Sna& 'D is an e6a#&le o- "snare

&rotein

(as crucial role in rec!cling clat(rinde&endent ligands in @rolast

-unctions as negati2e #odulator o-

neurotrans#itter release (as a role in #ediating Golgi trac/ing (as a role in e&ider#al diEerentiation


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1ac2 of %N" &0 leads to: Anor#al secretion o- la#ellar granules

Ic(t!osi-or# 4(enot!&e


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%U++"R/ 3a 'A #utation causes distured

#elanoso#e #o2e#ent and secretor!l!soso#e o- c!toto6ic "cells+ targeting , and

is associated )it( Griscelli S!ndro#e "!&e II. 3a :A regulation is aEected ! #utationsassociated )it( neurode2eloental de-ectscausing


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CONC1U%ION

%esicular trans&ort does not al)a!s &roceed)it(out a)s. "(ere are ti#es )(erein#utations in s&eci@c &roteins suc( as 3a

'A, 3a :A, and S$A4 'D+ aEect 2esiculartrans&ort )it(in cells t(ere-ore causingdiEerent disorders.

7o)e2er, t(ese studies lead to t(e

o&&ortunit! o- ne) treat#ents since saiddisorders still (a2e no s&eci@c curea2ailale.


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R$!$R$NC$% Fuc(s"ele#, . et. al. '011+. >9$IK S!ndro#e 3esults -ro#

Losso-Function Mutations in S$A4'D. Br J Dermatol, C10C1C.

Gissen, 4. and 9. Ma(er. '00+. >argos and Genes Insig(ts

into %esicular "rans&ort -ro# In(erited 7u#an isease. J MedGenet, 55555.

OHneill, M. '01:+. Cerebral dysgenesis, Neuropathy, Ichthyosis, andPalmoplantar Keratoderma Syndrome. Retrieved 01 December 20015 fromhttp://www.omim.org/entry/609528

Or&(anet. '00C+. CEDNIK S!ndro#e Summary. 3etrie2ed 01ece#er '015 -ro# (tt&*))).or&(a.netconsorcgiinO>J96&.&(&LngGB96&ertCCC:1


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TH"N. /OU !OR 1I%T$NING3

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Cargos and Genes