Homer protein homolog 1 or Homer1 is a neuronal
protein that in humans is encoded by the ''HOMER1''
gene.
Other names are Vesl and PSD-Zip45.
Structure
Homer1
protein has an N-terminal
EVH1 domain, involved in protein interaction, and a C-terminal
coiled-coil
A coiled coil is a structural motif in proteins in which 2–7
alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...
domain involved in self association. It consists of two major
splice variants, short-form (Homer1a) and long-form (Homer1b and c). Homer1a has only EVH1 domain and is monomeric while Homer1b and 1c have both EVH1 and coiled-coil domains and are tetrameric.
The coiled-coil can be further separated into N-terminal half and C-terminal half. The N-terminal half of the coiled-coil domain is predicted to be a parallel dimer while the C-terminus half is a hybrid of dimeric and anti-parallel tetrameric coiled-coil. As a whole, long Homer is predicted to have a dumbbell-like structure where two pairs of EVH1 domains are located on two sides of long (~50 nm) coiled-coil domain.
Mammals have
Homer2 and
Homer3
Homer protein homolog 3 is a protein that in humans is encoded by the ''HOMER3'' gene.
Function
This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor func ...
, in addition to Homer1, which have similar domain structure. They also have similar alternatively spliced forms.
Tissue distribution
Homer1 is expressed widely in the
central nervous system as well as peripheral tissue including
heart,
kidney,
ovary
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
,
testis, and
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
. Subcellularly in neurons, Homer1 is concentrated in postsynaptic structures and constitutes a major part of the
postsynaptic density.
Function
EVH1 domain
interacts with PPXXF motif. This sequence motif exists in group 1
metabotrophic glutamate receptor (mGluR1 and mGluR5),
IP3 receptors (IP
3R),
Shank,
transient receptor potential canonical (TRPC) family channels,
drebrin,
oligophrenin,
dynamin3,
CENTG1, and
ryanodin receptor.
Through its tetrameric structure, long forms of Homer (such as Homer1b and Homer1c) are proposed to cross link different proteins. For example, group 1 mGluR is crossed linked with its signaling downstream, IP
3 receptor.
Also, through crosslinking another multimeric protein Shank, it is proposed to comprise a core of the
postsynaptic density.
Notably, the expression of Homer1a is induced by neuronal activity while that of Homer1b and 1c are constitutive. Thus Homer1a is classified as an
immediate early gene. Homer1a, acts as a natural
dominant negative form that blocks interaction between long-forms and their ligand proteins by competing with the EVH1 binding site on the ligand proteins. In this way, the short form of Homer uncouples mGluR signaling and also shrinks
dendritic spine structure.
Therefore, the short form of Homer is considered to be a part of a mechanism of
homeostatic plasticity
In neuroscience, homeostatic plasticity refers to the capacity of neurons to regulate their own excitability relative to network activity. The term homeostatic plasticity derives from two opposing concepts: 'homeostatic' (a product of the Greek w ...
that dampens the neuronal responsiveness when input activity is too high. The long form Homer1c plays a role in
synaptic plasticity and the stabilization of synaptic changes during
long-term potentiation.
The coiled-coil domain is reported to interact with
syntaxin13 and activated
Cdc42. The interaction with Cdc42 inhibit the activity of Cdc42 to remodel dendritic spine structure.
Rapid antidepressant effects
Homer1a switches mGluR5 signaling to increase AMPA receptor activity for the rapid antidepressant actions of sleep deprivation.
See also
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HOMER2
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HOMER3
Homer protein homolog 3 is a protein that in humans is encoded by the ''HOMER3'' gene.
Function
This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor func ...
References
Further reading
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{{PDB Gallery, geneid=9456
EVH1 domain