BIOCHEMISTRY & CELL BIOLOGY

SELF-INSTRUCTION MODULE 3-3

THE LYSOSOME

DR. RICHARD HANN

DEPARTMENT OF BIOCHEMISTRY
2013 by Universidad Central del Caribe
All rights reserved
PURPOSE & SCOPE OF THE SELF-INSTRUCTION MODULES

Due to the limitation of faculty-student contact hours, it is not

possible to present in the classroom all of the concepts in
Biochemistry & Cell Biology that the student must learn. The
self-instruction modules (SIMs) are designed to provide,
within a student-centered electronic format, a structured
presentation of essential concepts & information that cannot
be presented in the classroom. Each SIM is a power-point
presentation that the student may access via the Blackboard
BCB course site at his or her convenience. Studying each of
the SIMs is compulsory. The material on each SIM is tested on
the subsequent examinations.
 LEARNING OBJECTIVES OF THIS MODULE
Upon completion of this module the student should be able to:

1. Characterize lysosome structure and morphology

2. Explain the role of acid hydrolases in normal lysosome function

and in lysosomal storage diseases

3. Describe how lysosomes are formed and acquire their enzymes

4. Describe the endocytosis & autophagy mechanisms including the

main proteins involved & the role of lysosomes in this process
CONTENTS OF THIS MODULE:

1. LYSOSOME MORPHOLOGY

2. LYSOSOME BIOCHEMISTRY

3. LYSOSOME FUNCTIONS

4. LYSOSOME BIOGENESIS
 LYSOSOME MORPHOLOGY

LYSOSOMES ARE ENCLOSED BY A

SINGLE MEMBRANE

LYSOSOME SHAPE IS
USUALLY SPHERICAL

ELECTRON MICROGRAPH OF A LIVER

CELL LYSOSOME STAINED WITH AN ACID
PHOSPHATASE SUBSTRATE + PbCl2
LYSOSOME SIZE IS VARIABLE
OR POLYMORPHIC

PRIMARY LYSOSOMES ARE

ABOUT 50nm IN DIAMETER

THEY ARE ALSO CALLED

NASCENT LYSOSOMES

NASCENT = NEWBORN

200m
 SECONDARY LYSOSOMES ARE
FROM 50 TO > 1000nm IN DIAMETER

THEY ARE ALSO CALLED

POST-FUSION ENDOLYSOSOMES

THE LUMEN OF 2o LYSOSOMES

MAY APPEAR HETEROGENEOUS

THE UNSTAINED MATERIAL IN THIS

LYSOSOME IS UNDEGRADED CELLULOSE

200m
 LYSOSOMES ARE FOUND IN
THE CYTOPLASM OF ALL CELLS
(INCLUDING ERYTHROCYTES)

LYSOSOMES NUMBER
ABOUT 300 PER CELL

LYSOSOMES ARE
ESPECIALLY ABUNDANT IN
PHAGOCYTIC CELLS

USING STANDARD MICROSCOPIC

METHODS LYSOSOMES ARE EASILY
CONFUSED WITH PEROXISOMES ELECTRON MICROGRAPH OF
HEPATOCYTE CYTOPLASM
 pH INDICATOR DYES CAN BE
USED TO IDENTIFY LYSOSOMES

THE LYSOSOMAL LUMEN

STAINS ACIDIC (pH < 7) USING
pH INDICATOR DYES

THE PEROXISOMAL LUMEN

IS NEUTRAL (pH 7)

LYSOSOMES (RED)

LEUKOCYTE TREATED WITH A RED

ACIDOPHORIC DYE (LYSOTRACKER)
RED @ pH < 6
LYSOSOMAL ENZYME-SPECIFIC STAINS CAN BE
USED TO IDENTIFY LYSOSOMES

ELECTRON MICROGRAPH OF A LIVER CELL

TREATED WITH A LYSOSOMAL ACID
PHOSPHATASE SUBSTRATE + PbCl2 TO
PRECIPITATE LEAD PHOSPHATE

THE ELECTRON DENSE MATERIAL IS

LEAD PHOSPHATE (PbHPO4)

THE ELECTRON LUCENT MATERIAL IS

UNDEGRADED CELLULOSE
 LYSOSOME BIOCHEMISTRY

THE LYSOSOME HAS AN ACIDIC LUMEN

pH 5 vs CYTOSOL pH 7.4

THIS MEANS THE LUMINAL PROTON CONCENTRATION

IS 300 TIMES GREATER THAN THE CYTOPLASMIC
PROTON CONCENTRATION

[H+]L / [H+]C = 300/1

LYSOSOMAL LUMEN ACIDITY
IS MAINTAINED BY AN
ATP-DEPENDENT PROTON PUMP
THE ATP-DEPENDENT PROTON PUMP
VACUOLAR ATPase
ALSO CALLED A VACUOLAR ATPase pH 7.4

THE VACUOLAR ATPase STRUCTURE &

MECHANISM ARE VERY SIMILAR TO
THE MITOCHONDRIAL ATP SYNTHASE:
A ROTARY MOTOR
(BUT RUN IN REVERSE!)

ATP HYDROLYSIS TRANSFERS PROTONS

FROM THE CYTOSOL INTO THE
LYSOSOMAL LUMEN

pH 5
LYSOSOMAL LUMEN

THE VACUOLAR ATPase

PROTON PUMP
 EACH LYSOSOME CONTAINS ABOUT
50 DIFFERENT LYSOSOMAL HYDROLASES
ALL LYSOSOMAL ENZYMES ARE ACID HYDROLASES WITH pH OPTIMA < 7
BUT MOST ARE ALSO ACTIVE @ pH 7.4

THE LYSOSOMAL HYDROLASES ARE ABLE

TO DEGRADE ALMOST ALL (BUT NOT ALL!)
OF THE MACROMOLECULES
THAT THE LYSOSOME INGESTS

A + H2O B+C
 THERE ARE 4 MAIN CLASSES OF LYSOSOMAL HYDROLASES

1. ESTERASES (14) BOND HYDROLYZED: EXAMPLES:

CARBONYL ESTER R C O R ACID LIPASE

PHOSPHOLIPASES
O
O

PHOSPHATE ESTER R O P O R RIBONUCLEASE

DEOXYRIBONUCLEASE
O SPHINGOMYELINASE
O

SULFATE ESTER R O S O R IDURONATE SULFATASE

O
2. AMIDASES (6) BOND HYDROLYZED: EXAMPLES:

CARBONYL AMIDE R C NH R CERAMIDASE

O
O

PHOSPHOAMIDE R O P NH R PHOSPHOAMIDASE

O
O

SULFAMIDE R O S NH R HEPARIN SULFAMIDASE

O
3. PROTEASES (15) BOND HYDROLYZED: EXAMPLES:
R
COLLAGENASE
PEPTIDE BOND C C NH C
ELASTASE
O R

LYSOSOMES CAN DEGRADE ANY POLYPEPTIDE

PROTEASE SPECIFICITY DEPENDS ON THE R OR R GROUP

4. GLYCOSIDASES (15) BOND HYDROLYZED: EXAMPLES:

ACID MALTASE
(1 4) GLUCOSIDASE
GLYCOSIDIC
BOND -L-IDURONIDASE
GLUCOCEREBROSIDASE
GLUCOSE-(1 4)-GLUCOSE GALACTOCEREBROSIDASE
HUMAN LYSOSOMES DO NOT HAVE A (1 4) GLUCOSIDASE
THEY CANNOT DEGRADE CELLULOSE WHICH HAS
A GLUCOSE-(1 4)-GLUCOSE BOND

CELLULOSE IS THE MOST ABUNDANT

POLYSACCHARIDE FOUND IN NATURE

THEY ALSO CANNOT DEGRADE CHITIN WHICH HAS

A GLCNAc-(1 4)-GLCNAc BOND

CHITIN IS THE SECOND MOST ABUNDANT UNDIGESTED

POLYSACCHARIDE FOUND IN NATURE MATERIAL
IS CELLULOSE
 CLINICAL CORRELATION
LYSOSOMAL STORAGE DISEASES
LYSOSOMAL STORAGE DISEASES ARE CAUSED BY
INDIVIDUAL LYSOSOMAL HYDROLASE DEFICIENCIES
SOME IMPORTANT EXAMPLES:
DEFICIENT HYDROLASE: LYSOSOMAL STORAGE DISEASE:
ACID MALTASE POMPE DISEASE (GSD TYPE 2)
ACID LIPASE WOLMAN DISEASE
SPHINGOMYELINASE NIEMANN-PICK DISEASE (TYPE A)
GLUCOCEREBROSIDASE GAUCHER DISEASE
GALACTOCEREBROSIDASE KRABBE DISEASE

FOAM CELLS FROM A PATIENT

WITH NIEMANN-PICK DISEASE

THE FOAM IS LYSOSOMES FILLED

WITH UNDEGRADED SPHINGOMYELIN
OTHER IMPORTANT EXAMPLES OF LYSOSOMAL STORAGE DISEASES:

DEFICIENT HYDROLASE: LYSOSOMAL STORAGE DISEASE:

HEXOSAMINIDASE A TAY-SACHS DISEASE
GM1--GALACTOSIDASE GM1 GANGLIOSIDOSIS
-L-IDURONIDASE HURLERS SYNDROME
IDURONIDATE SULFATASE HUNTERS SYNDROME

FUNDOSCOPIC PICTURE OF RETINA LYSOSOMES FROM A PATIENT

OF TAY-SACHS DISEASE PATIENT WITH GM1 GANGLIOSIDOSIS
SHOWING CHARACTERISTIC
CHERRY-RED SPOT
 LYSOSOME FUNCTIONS

THE BASIC FUNCTION OF LYSOSOMES

IN ALL CELLS IS THE
HYDROLYTIC DEGRADATION
OF MACROMOLECULES A + H2O B+C
 LYSOSOMES FUNCTION IN ENDOCYTOSIS & AUTOPHAGY

receptor- ENDOCYTOSIS IS THE

mediated INTERNALIZATION OF
endocytosis
EXTRACELLULAR MATERIAL
X
X XXX
XX X X X
XXX
AUTOPHAGY IS THE
LYSOSOMAL DEGRADATION OF
fluid-phase
INTRACELLULAR STRUCTURES
endocytosis
 ENDOCYTOSIS INCLUDES AT LEAST 3 DISTINCT PATHWAYS
ALL OF WHICH TERMINATE IN FUSION WITH LYSOSOMES
receptor-
mediated 1. RECEPTOR-MEDIATED
endocytosis
ENDOCYTOSIS
X
X XXX
XX X X X 2. FLUID-PHASE
XXX
ENDOCYTOSIS

fluid-phase 3. PHAGOCYTOSIS
endocytosis
 RECEPTOR-MEDIATED ENDOCYTOSIS IS CLATHRIN-DEPENDENT

receptor- INTERNALIZED
Clathrin
mediated CLATHRIN-COATED VESICLES ARE
endocytosis
UNCOATED IN AN
X
ATP-DEPENDENT PROCESS
X XXX
XX X X X ATP
XXX UNCOATED ENDOSOMES DOCK &
FUSE WITH LYSOSOMES

fluid-phase RECEPTOR-MEDIATED
endocytosis
ENDOCYTOSIS IS ESPECIALLY
IMPORTANT IN CELL NUTRIENT
UPTAKE

EXAMPLES:
THE LDL RECEPTOR
THE TRANSFERRIN RECEPTOR
 FLUID-PHASE ENDOCYTOSIS IS A CONSTITUTIVE PROCESS

THE PROCESS IS
receptor-
mediated NOT RECEPTOR-MEDIATED
endocytosis
THE PROCESS IS
X
X XXX CLATHRIN-INDEPENDENT
XX X X X
XXX
ENDOSOMES DOCK & FUSE WITH
LYSOSOMES
fluid-phase
endocytosis
FLUID-PHASE ENDOCYTOSIS IS
ALSO CALLED PINOCYTOSIS
 PHAGOCYTOSIS OCCURS ONLY IN SPECIALIZED PHAGOCYTIC CELLS
LIKE MACROPHAGES & NEUTROPHILS
receptor-
mediated PHAGOCYTOSIS INVOLVES LARGE
endocytosis PARTICLES, MICROORGANISMS
OR OTHER CELLS
X
X XXX phagocytosis
XX X X X
XXX THE PROCESS IS
RECEPTOR-MEDIATED BUT
CLATHRIN-INDEPENDENT
fluid-phase
endocytosis LARGE UNCOATED VESICLES
(PHAGOSOMES) HAVE VISIBLE
CONTENTS UNDER LM

PHAGOSOMES DOCK & FUSE

WITH LYSOSOMES
 EXAMPLES OF PHAGOCYTOSIS

ELECTRON MICROGRAPH OF A
PSEUDOPOD FORMATION IS
MACROPHAGE PHAGOCYTOSING
RECEPTOR-MEDIATED BUT
TWO ERYTHROCYTES
CLATHRIN-INDEPENDENT
ARROWS INDICATE EDGES OF
MACROPHAGE PSEUDOPODS
IN AUTOPHAGY A TARGETED CELL STRUCTURE IS ENCLOSED BY A DOUBLE
MEMBRANE TO PRODUCE AN AUTOPHAGOSOME
receptor-
mediated
endocytosis

X
X XXX
XX X X X
XXX

fluid-phase
endocytosis

THE AUTOPHAGOSOME THEN

autophagy FUSES WITH LYSOSOMES
THE CONTENTS ARE DEGRADED &
RECYCLED
 LYSOSOME-RELATED ORGANELLES
(aka SECRETORY LYSOSOMES)
LROs HAVE SPECIALIZED FUNCTIONS IN
CERTAIN CELL TYPES

MELANOSOMES IN MELANOCYTES

SECRETORY LYSOSOMES IN OSTEOCLASTS

FOR BONE RESORPTION

SECRETORY LYSOSOMES IN MELANOSOMES HOLD MELANIN

CYTOTOXIC LYMPHOCYTES FOR SECRETION & UPTAKE BY
KERATINOCYTES
DENSE GRANULES IN PLATELETS
ACROSOMES IN SPERMATOZOA
LYSOSOMAL
ENZYMES

UPON CONTACTING THE EGG THE

ACROSOME RELEASES ITS ENZYMES

THESE ENZYMES DIGEST THE ZONA

PELLUCIDA ALLOWING THE SPERM
NUCLEUS TO ENTER THE EGG

A SPERMATOZOON
 LYSOSOME BIOGENESIS
LYSOSOMAL ENZYME PRECURSORS ARE MADE IN THE ER &
THEN TARGETED TO LYSOSOMES VIA THE GOLGI APPARATUS

1o Lysosome
IN THE cis-GOLGI A MANNOSE RESIDUE ON THE HYDROLASE
PRECURSOR IS CONVERTED INTO MANNOSE-6-PHOSPHATE

1o Lysosome
THE LYSOSOMAL ENZYME
PRECURSORS THEN MOVE
THROUGH THE GOLGI
APPARATUS
 IN THE trans-GOLGI MANNOSE-6-PHOSPHATE-LABELED
PRECURSORS BIND TO A MANNOSE-6-PHOSPHATE RECEPTOR

Trans-Golgi
Lumen

M6P-R

Cytosol 1o Lysosome

THE MAJOR MANNOSE-6-P RECEPTOR

IS A MEMBRANE-BOUND HOMODIMER
& BINDS 2 LYSOSOMAL PRECURSORS
VESICLES WITH M6P-RECEPTOR-BOUND LYSOSOMAL
ENZYME PRECURSORS BUD FROM THE trans-GOLGI

1o Lysosome

BUD & VESICLE FORMATION IS CLATHRIN-DEPENDENT

 UNCOATED VESICLES WITH RECEPTOR-BOUND PROTEINS
FUSE TOGETHER TO FORM 1o LYSOSOMES

AN ATP-DEPENDENT PROTON PUMP

LOWERS THE pH IN THE LYSOSOMES

THE LOW pH IN THE LYSOSOMES MAKES

THE ENZYME
PRECURSORS DISSOCIATE FROM THE
M6P RECEPTOR

PHOSPHATE REMOVAL PRODUCES MATURE

ACTIVE HYDROLASES 1o Lysosome
 VESICLES WITH EMPTY M6P RECEPTORS BUD FROM
THE LYSOSOMES AND RECYCLE BACK TO THE trans-GOLGI

1o Lysosome

RECEPTOR RECYCLING IS NOT CLATHRIN-DEPENDENT

THE ADDITION OF A PHOSPHATE GROUP TO THE MANNOSE ON THE LYSOSOMAL
HYDROLASE IN THE cis-GOLGI IS A 2 STEP PROCESS

UDP-N-ACETYLGLUCOSAMINE (UDP-GlcNAc)
PROVIDES THE PHOSPHATE GROUP

UDP-GlcNAc
 TWO cis-GOLGI ENZYMES ARE REQUIRED TO ADD THE PHOSPHATE

GlcNAc PHOSPHOTRANSFERASE (PT) Mannose GlcNAc

RECOGNIZES THE LYSOSOMAL
HYDROLASE & THEN USES
UDP-GlcNAc TO ADD GlcNAc-P ONTO
C6 OF A MANNOSE RESIDUE
RELEASING UMP
PT PG
GlcNAc PHOSPHOGLYCOSIDASE (PG)

THEN HYDROLYZES OFF GlcNAc

LEAVING ONLY PHOSPHATE ON
C6 OF THE MANNOSE RESIDUE
PT
GlcNAc = N-acetyl-glucosamine

PG
GlcNAc PHOSPHOTRANSFERASE (PT) HAS 2 CRITICAL DOMAINS:
THE CATALYTIC SITE & THE HYDROLASE RECOGNITION SITE

A 3-DIMENSIONAL MOTIF OR SIGNAL PATCH ON THE

HYDROLASE BINDS IN THE RECOGNITION SITE SO THAT
THE MANNOSE RESIDUE EXTENDS INTO THE CATALYTIC SITE

cis-Golgi
ONLY LYSOSOMAL PROTEINS HAVE
THIS SIGNAL PATCH
 UDP-GlcNAc ALSO BINDS IN THE CATALYTIC SITE
PT THEN TRANSFERS GlcNAc-P ONTO MANNOSE C6 & RELEASES UMP

cis-Golgi
PG

UPON RELEASE OF THE LYSOSOMAL HYDROLASE FROM PT

PG USES WATER TO CUT OFF GlcNAc
 CLINICAL CORRELATION
INCLUSION CELL DISEASE
I-CELL DISEASE OR MUCOLIPIDOSIS TYPE II

CLINICAL MANIFESTATIONS
COARSE HURLER-LIKE FACIAL FEATURES
HIGH FOREHEAD, PUFFY EYELIDS, PROMINENT I-CELL DISEASE HURLER
EPICANTHAL FOLDS, FLATTENED NASAL BRIDGE PATIENT SYNDROME
MACROGLOSSIA, GINGIVAL HYPERTROPHY PATIENT
(OFTEN MISDIAGNOSED AS HURLER SYNDROME*)
CORNEAL
BILATERAL CORNEAL OPACITIES OPACITY IN AN
I-CELL DISEASE
POOR GROWTH & PSYCHOMOTOR RETARDATION PATIENT
RESTRICTED JOINT MOBILITY
HEPATOMEGALY & CARDIOMEGALY

LAB FINDINGS
ABNORMALLY HIGH LEVELS OF LYSOSOMAL
ENZYMES IN THE BLOOD

*HURLER SYNDROME IS A LYSOSOMAL STORAGE DISEASE

CAUSED BY DEFICIENCY OF -L-IDURONIDASE
I-CELL DISEASE PATIENT AT 2 YEARS
 PHASE-CONTRAST & ELECTRON MICROSCOPY
REVEALS CELLS FILLED WITH NUMEROUS SMALL
MEMBRANE-LINED INCLUSIONS WHICH ARE
PHASE-DENSE BUT ELECTRON-LUCENT

THE DENSE INCLUSIONS ARE LYSOSOMES

& GIVE THIS DISEASE ITS NAME

PHASE-CONTRAST MICROGRAPH
OF FIBROBLASTS FROM AN
I-CELL DISEASE PATIENT

I-CELL DISEASE IS CAUSED BY A DEFECT IN LYSOSOME BIOGENESIS

I-CELL DISEASE PATIENTS HAVE A MUTATION IN THE
GlcNAc PHOSPHOTTRANSFERASE (PT) CATALYTIC SITE

cis-Golgi PT IS NON-FUNCTIONAL SO
PRE-LYSOSOMAL PROTEINS
DO NOT GET LABELED!

X X X
UNLABELED HYDROLASES ARE NOT SEGREGATED TO THE LYSOSOME BUT INSTEAD
ENTER THE SECRETORY PATHWAY & ARE SECRETED FROM THE CELL
THIS MAKES BLOOD LYSOSOMAL HYDROLASE
LEVELS MUCH HIGHER THAN NORMAL THE LYSOSOMES DO NOT
ACQUIRE HYDROLASES
SECRETORY
PATHWAY

X X X
X
X
1o Lysosome

LYSOSOMES FILL UP WITH UNDEGRADED

MACROMOLECULES & FORM DENSE INCLUSIONS
 CLINICAL CORRELATION
HERMANSKY-PUDLAK SYNDROME (HPS)
HPS IS A DISEASE OF LYSOSOME BIOGENESIS
CLINICAL MANIFESTATIONS:

OCULOCUTANEOUS ALBINISM IS DUE TO

DEFECTIVE MELANOSOME FORMATION
MELANIN SYNTHESIS IS NOT AFFECTED

BLEEDING DISORDER
EASY BRUISABILITY & NOSEBLEEDS
EXCESS MENSTRUATION & POST-PARTUM
HEMORRHAGE IN FEMALES PUERTO RICAN GIRL WITH HPS
DEFECTIVE PLATELET DENSE BODY FORMATION

INTESTINE: CHRONIC ENTEROCOLITIS NORMAL HPS

KIDNEYS: RENAL FAILURE

LUNG: INSTITIAL PULMONARY FIBROSIS UNSTAINED RETINA (UPPER)

(THIS IS THE CAUSE OF DEATH IN ABOUT 50%) & CHOROID LAYER (LOWER)
SPECIMENS TAKEN AT AUTOPSY
FROM NORMAL & HPS PATIENTS
HPS IS THE MOST COMMON MONOGENIC
DISORDER IN PUERTO RICO

HPS ACCOUNTS FOR 80% OF ALL ALBINOS

LIVING IN PUERTO RICO

0.06% (1/1800) OF PUERTO RICANS LIVING

IN THE NW CORNER OF PR HAD HPS
IN A 1990 SURVEY BY DHAL et al.

4% OF THE POPULATION WERE

HETEROZYGOUS CARRIERS OF THE MOST
COMMON GENE DEFECT
HPS CONFERENCE HELD IN PR
THIS DEFECT IS IN THE HPS-1 GENE

(BUT NOT ALL CASES OF HPS ARE CAUSED BY A

DEFECT IS IN THE HPS-1 GENE)
 THE HPS-1 GENE ON CHROMOSOME 10 ENCODES A
700 AMINO ACID (79kD) HPS-1 PROTEIN

MOST HPS PATIENTS STUDIED IN PR ARE

HOMOZYGOUS FOR A 16bp REPEAT INSERT IN THE HPS-1 GENE

THIS INSERT CAUSES A FRAME-SHIFT THAT PRODUCES A TRUNCATED HPS-1

PROTEIN WITH LOSS OF FUNCTION OF THE

ALTERNATIVE
SPLICING
MOST COMMON
THE HPS-1 GENE PR MUTATION
THE 11 OTHER IDENTIFIED MUTATIONS THAT LEAD TO HPS ARE INDICATED

3 UTR

LONG ISOFORM (79kD) MOST COMMON

PR MUTATION
 THE HPS-1 PROTEIN IS ESSENTIAL FOR
LRO FORMATION IN CERTAIN CELLS
HPS-1 & HPS-4 FORM A BIOGENESIS OF LYSOSOME-
RELATED ORGANELLES COMPLEX 3 (BLOC-3)

BLOC-3 FUNCTIONS AS A GUANINE NUCLEOTIDE

HPS-1
EXCHANGE FACTOR FOR Rab32 & Rab38

Import
Rab 32 & Rab38 ARE MONOMERIC G-
melanin
PROTEINS EXPRESSED ALMOST
synthesis
EXCLUSIVELY IN MELANOCYTES
proteins
ACTIVE Rab 32 & Rab38 ARE NEEDED
TO IMPORT PROTEINS INVOLVED IN
MELANIN SYNTHESIS SUCH AS
TYROSINASE

ACTION OF BLOC-3 IN MELANOCYTES

MULTIPLE PROTEINS ARE INVOLVED IN MELANOSOME BIOGENESIS
LOSS-OF-FUNCTION OF ANY OF THEM CAN PRODUCE HPS
OR AN HPS-LIKE DISEASE

melanin-synthesis proteins
LYSOSOMES
HPS-1
HPS-5 HPS-2
HPS-4
HPS-7 HPS-3 HPS-6 (AP3)

Rab32/38

BIOGENESIS OF MELANOSOMES IN MELANOCYTES

END OF SIM 3-3