Nectin
Encyclopedia
Nectins and Nectin-like molecules (Necl) are families of cellular adhesion molecules involved in Ca2+
-independent cellular adhesion.
Nectins are ubiquitously expressed and have adhesive roles in a wide range of tissues such as the adherens junction
of epithelia or the chemical synapse
of the neuronal tissue.
, nectin-2
, nectin-3
and nectin-4. These four family members have also been found in most other well studies mammals. Also, five Necls have been identified, these are: Necl-1
, Necl-2, Necl-3, Necl-4 and Necl-5
.
s, a single transmembrane helix and an intracellular domain. For all nectins the intracellular domain can bind a scaffold protein
named afadin (the product of the MLLT4
gene).
All nectins and Necls can form homo-cis dimers, meaning a dimer of two alike molecules on the same cell membrane. Following the homo-dimer formation they can trans-interact in an either heterophilic or homophilic manner. The network of the nectin and Necl trans-interactions has been characterized.. In general, heterophilic trans-interactions have higher affinity than homophilic ones.
Nectins and Necls can also recruit cadherin
s to enhance binding.
nectin-1 : PVRL1
(Poliovirus receptor-related 1), HveC (herpesvirus entry mediator C) , CD111 (Cluster of Differentiation 111)
nectin-2 : PVRL2
(Poliovirus receptor-related 2), HveB (herpesvirus entry mediator B), CD112 (Cluster of Differentiation 112)
nectin-3 : PVRL3
(Poliovirus receptor-related 3)
nectin-4 : no other names
necl-1 : CADM3
(Cell adhesion molecule 3), TSLL1 (TSLC1-like 1), SynCAM3 (Synaptic cell adhesion molecule 3), IGSF4B (Immunoglobulin super family member 4B)
necl-2 : CADM1 (Cell adhesion molecule 1), TSLC1 (Tumor suppressor in lung cancer 1), SynCAM1 (Synaptic cell adhesion molecule 1), IGSF4 (Immunoglobulin super family member 4), sgIGSF (Spermatogenic immunoglobulin superfamily) , RA175
necl-3 : SynCAM2 (Synaptic cell adhesion molecule 2)
necl-4 : TSLL2 (TSLC1-like 2), SynCAM4 (Synaptic cell adhesion molecule 1)
necl-5 : Tage4, PVR (Poliovirus receptor), CD155
Nectin-1 and nectin-3 have been shown to be involved in cellular adhesion in some neuronal synapses. Unlike many other cellular adhesion molecules they do not distribute evenly on axonal and dendritic side of the synapse. Instead, Nectin-1 is primarily found on the axonal side and nectin-3 primarily on the dendritic side.
Recently, it has been found that nectin-4 can be found in the serum of patients suffering from lung cancer. This has led to speculations that this protein might be involved in some developing cancers and might even have a pharmaceutical potential.
Also, it has been well known for some time now, that necl-2 is down regulated in a variety of cancers. This is why necl-2 is also known as Tumor suppressor in lung cancer 1 (TSLC1).
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
-independent cellular adhesion.
Nectins are ubiquitously expressed and have adhesive roles in a wide range of tissues such as the adherens junction
Adherens junction
Adherens junctions are protein complexes that occur at cell–cell junctions in epithelial tissues, usually more basal than tight junctions...
of epithelia or the chemical synapse
Chemical synapse
Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...
of the neuronal tissue.
Diversity
So far four nectins have been identified in humans, namely nectin-1PVRL1
Poliovirus receptor-related 1 , also known as PVRL1, is a human gene that encodes a protein of immunoglobulin superfamily also considered a member of the nectins . It is a membrane protein with three extracellular immunoglobulin domains, a single transmembrane helix and a cytoplasmic tail...
, nectin-2
PVRL2
Poliovirus receptor-related 2 , also known as PVRL2 and CD112 , is a human gene.-External links:...
, nectin-3
PVRL3
Poliovirus receptor-related 3 , also known as PVRL3 and CD113 , is a human gene.-Interactions:PVRL3 has been shown to interact with MLLT4, PARD3, and PTPmu ....
and nectin-4. These four family members have also been found in most other well studies mammals. Also, five Necls have been identified, these are: Necl-1
CADM3
Cell adhesion molecule 3 is a protein that in humans is encoded by the CADM3 gene.-Further reading:...
, Necl-2, Necl-3, Necl-4 and Necl-5
CD155
CD155 also known as the poliovirus receptor is a protein that in humans is encoded by the PVR gene.- Function :CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily...
.
Structure
All nectins and all Necls share the same overall structure defined by three extra cellular immunoglobulin domainImmunoglobulin domain
The immunoglobulin domain is a type of protein domain that consists of a 2-layer sandwich of between 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek key topology....
s, a single transmembrane helix and an intracellular domain. For all nectins the intracellular domain can bind a scaffold protein
Scaffold protein
In biology, scaffold proteins are crucial regulators of many key signaling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes...
named afadin (the product of the MLLT4
MLLT4
Afadin is a protein that in humans is encoded by the MLLT4 gene.-Interactions:MLLT4 has been shown to interact with F11 receptor, RAP1A, LMO2, EPHB3, RAP1GAP, PVRL1, PVRL3, USP9X, SORBS1, BCR gene, Tight junction protein 1, Profilin 1, HRAS and SSX2IP.-Further reading:...
gene).
All nectins and Necls can form homo-cis dimers, meaning a dimer of two alike molecules on the same cell membrane. Following the homo-dimer formation they can trans-interact in an either heterophilic or homophilic manner. The network of the nectin and Necl trans-interactions has been characterized.. In general, heterophilic trans-interactions have higher affinity than homophilic ones.
Nectins and Necls can also recruit cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...
s to enhance binding.
Nomenclature controversy
Since the research of nectins has been approached from several angles there is still some controversy about the names of these proteins and the genes encoding them. The idea of grouping these proteins into nectins and Necls originates from Dr. Youhsimi Takais early studies of the proteins. Nectins and Necls are much related in function and protein structure and have been found to interact in a variety of way, which it is why it makes good sense to define them as families. However, if you consider the sequence of the genes encoding the proteins an alternative way of naming the proteins also make sense as pointed out by Thomas Biederer. Alternative names for nectins and Necls are listed below.nectin-1 : PVRL1
PVRL1
Poliovirus receptor-related 1 , also known as PVRL1, is a human gene that encodes a protein of immunoglobulin superfamily also considered a member of the nectins . It is a membrane protein with three extracellular immunoglobulin domains, a single transmembrane helix and a cytoplasmic tail...
(Poliovirus receptor-related 1), HveC (herpesvirus entry mediator C) , CD111 (Cluster of Differentiation 111)
nectin-2 : PVRL2
PVRL2
Poliovirus receptor-related 2 , also known as PVRL2 and CD112 , is a human gene.-External links:...
(Poliovirus receptor-related 2), HveB (herpesvirus entry mediator B), CD112 (Cluster of Differentiation 112)
nectin-3 : PVRL3
PVRL3
Poliovirus receptor-related 3 , also known as PVRL3 and CD113 , is a human gene.-Interactions:PVRL3 has been shown to interact with MLLT4, PARD3, and PTPmu ....
(Poliovirus receptor-related 3)
nectin-4 : no other names
necl-1 : CADM3
CADM3
Cell adhesion molecule 3 is a protein that in humans is encoded by the CADM3 gene.-Further reading:...
(Cell adhesion molecule 3), TSLL1 (TSLC1-like 1), SynCAM3 (Synaptic cell adhesion molecule 3), IGSF4B (Immunoglobulin super family member 4B)
necl-2 : CADM1 (Cell adhesion molecule 1), TSLC1 (Tumor suppressor in lung cancer 1), SynCAM1 (Synaptic cell adhesion molecule 1), IGSF4 (Immunoglobulin super family member 4), sgIGSF (Spermatogenic immunoglobulin superfamily) , RA175
necl-3 : SynCAM2 (Synaptic cell adhesion molecule 2)
necl-4 : TSLL2 (TSLC1-like 2), SynCAM4 (Synaptic cell adhesion molecule 1)
necl-5 : Tage4, PVR (Poliovirus receptor), CD155
CD155
CD155 also known as the poliovirus receptor is a protein that in humans is encoded by the PVR gene.- Function :CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily...
Clinical relevance
Even though no pharmaceutical products released so far target any nectins or Necls, some discoveries have intensified the clinical relevance of these proteins.Nectin-1 and nectin-3 have been shown to be involved in cellular adhesion in some neuronal synapses. Unlike many other cellular adhesion molecules they do not distribute evenly on axonal and dendritic side of the synapse. Instead, Nectin-1 is primarily found on the axonal side and nectin-3 primarily on the dendritic side.
Recently, it has been found that nectin-4 can be found in the serum of patients suffering from lung cancer. This has led to speculations that this protein might be involved in some developing cancers and might even have a pharmaceutical potential.
Also, it has been well known for some time now, that necl-2 is down regulated in a variety of cancers. This is why necl-2 is also known as Tumor suppressor in lung cancer 1 (TSLC1).