Lysosomal-associated membrane protein 1 (LAMP-1) also known as lysosome-associated membrane glycoprotein 1 and CD107a (Cluster of Differentiation 107a), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''LAMP1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. The human ''LAMP1'' gene is located on the long arm (q) of chromosome 13 at region 3, band 4 (13q34).
Lysosomal-associated membrane protein 1 is a
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
from a family of
Lysosome-associated membrane glycoproteins
Lysosome-associated membrane glycoproteins (LAMPs) are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. Structurally, the lamp proteins consist of two internally homologous lysosome-luminal d ...
.
The LAMP-1 glycoprotein is a type I
transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
which is expressed at high or medium levels in at least 76 different normal tissue cell types.
It resides primarily across l
ysosomal membranes,
and functions to provide
selectin
The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...
s with
carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
ligands
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
.
CD107a has also been shown to be a marker of
degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulo ...
on
lymphocytes
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
such as
CD8+
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
and
NK cells
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...
,
and may also play a role in
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
cell differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellula ...
and
metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
.
Structure
Residing primarily across lysosomal membranes, these glycoproteins consist of a large, highly
glycosylated
Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not alw ...
end with N-linked carbon chains on the luminal side of the membrane, and a short C-terminal tail
exposed to the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
.
The extracytoplasmic region contains a hinge-like structure which can form
disulphide bridges
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
homologous to those observed in human
immunoglobulin A
Immunoglobulin A (Ig A, also referred to as sIgA in its secretory form) is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other ty ...
.
Other characteristics of the structure of the LAMP-1 glycoproteins include:
* A
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
core of ~40kDa
* 18 sites to help with the addition of sugar chains
* Polylactosamine attachments which protect the glyocoprotein from degradation by lysosomal
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
s
* Significant quantities of polylactosaminoglycan and
sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.
The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...
to traverse the trans-
Golgi cisterna
A cisterna (plural cisternae) is a flattened membrane vesicle found in the endoplasmic reticulum and Golgi apparatus. Cisternae are an integral part of the packaging and modification processes of proteins occurring in the Golgi.
Function
Protei ...
e.
* poly-N-acetyllactosamine groups which are involved in interactions with
selectin
The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...
and other
glycan
The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate p ...
-binding proteins
Function
LAMP1 and
LAMP2 glycoproteins comprise 50% of all lysosomal membrane proteins,
and are thought to be responsible in part for maintaining lysosomal integrity, pH and
catabolism
Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...
.
The expression of LAMP1 and LAMP2 glycoproteins are linked, as deficiencies in ''LAMP1'' gene will lead to increased expression of LAMP2 glycoproteins.
The two are therefore thought to share similar functions ''in vivo''.
However, this makes the determining the precise function of LAMP1 difficult, because while the ''LAMP1'' deficient
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
is little different than the wild type due to ''LAMP2'' up regulation,
the ''LAMP1''/''LAMP2'' double deficient phenotype leads to
embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
nic lethality.
Although the LAMP1 glycoproteins primarily reside across lysosomal membranes, in certain cases they can be expressed across the plasma membrane of the cell.
Expression of LAMP1 at the cell surface can occur due to lysosomal
fusion
Fusion, or synthesis, is the process of combining two or more distinct entities into a new whole.
Fusion may also refer to:
Science and technology Physics
*Nuclear fusion, multiple atomic nuclei combining to form one or more different atomic nucl ...
with the cell membrane.
Cell surface expression of LAMP1 can serve as a ligand for
selectin
The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...
s
and help mediate cell-
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
.
Accordingly, cell surface expression of LAMP1 is seen in cells with migratory or invasive functions, such as
cytotoxic T cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
s,
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
s and
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s.
Cell surface expression of LAMP1 and LAMP2 is also often seen in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
cells,
particularly cancers with high metastatic potential, such as colon carcinoma and melanoma,
and has been shown to correlate with their metastatic potential.
Role in cancer
LAMP1 expression on the surface of tumor cells has been observed for a number of different cancer types, particularly in highly metastatic cancers such as
pancreatic cancer
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...
,
colon cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
and
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
.
The structure of LAMP1 correlates with
differentiation and metastatic potential
of tumor cells as it is thought to help mediate cell-cell adhesion
and
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
.
Indeed, the adhesion of some cancer cells to the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
is mediated by interactions between LAMP1 and LAMP2 and
E-selectin
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endothelial ...
and
galectin
Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, ''N''-acetyllactosamine (Galβ1-3GlcNAc or Galβ1-4GlcNAc), which can be bound to proteins by either N-linked glycosylation, N-linked o ...
s, with the LAMPs serving as ligands for the cell-adhesion molecules.
Cell membrane expression of LAMP-1 observed in the following cancer types:
* Human
fibrosarcoma
Fibrosarcoma (fibroblastic sarcoma) is a malignant mesenchymal tumour derived from fibrous connective tissue and characterized by the presence of immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform patte ...
,
*
Colon adenocarcinoma,
*
Melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
,
*
Pancreatic adenocarcinoma,
and
*
Astrocytoma
Astrocytomas are a type of brain tumor. They originate in a particular kind of glial cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usu ...
.
See also
*
Cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...
References
Further reading
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External links
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PDBe-KBprovides an overview of all the structure information available in the PDB for Human Lysosome-associated membrane glycoprotein 1
{{Peroxisomal proteins
Clusters of differentiation