Involvement of membrane palmitoylated protein 2 (MPP2) in the synaptic molecular complex at the mouse cerebellar

Tomoki Yamada1, Yurika Saitoh1,2, Kiyokazu Kametani1

  • 1Health Science Division, Department of Medical Sciences, Shinshu University Graduate School of Medicine, Science and Technology, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Insights

Membrane palmitoylated protein 2 (MPP2) localizes to cerebellar glomeruli postsynaptic regions, interacting with key synaptic proteins. MPP2 influences the distribution of Lin7, crucial for synaptic function in mouse cerebellum.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Protein 4.1G interacts with MPP6, Lin7, and CADM4 in peripheral nervous system Schwann cells.
  • MPP6 is a membrane skeletal protein involved in myelin formation.
  • MPP2 is a highly homologous protein to MPP6, necessitating investigation in the central nervous system.

Purpose of the Study:

  • To investigate the localization and protein interactions of MPP2 in the mouse cerebellum.
  • To understand MPP2's role in the postsynaptic region of cerebellar granule cells.
  • To elucidate MPP2's influence on synaptic protein distribution, particularly Lin7.

Main Methods:

  • Immunostaining for MPP2 in mouse cerebellum.
  • High-resolution confocal laser-scanning microscopy (Airyscan mode).
  • Immunoprecipitation analysis to identify protein complexes.
  • Comparison of wild-type and MPP2-deficient mouse cerebella.

Main Results:

  • MPP2 was detected in cerebellar glomeruli (CG) postsynaptic regions and adherens junctions.
  • MPP2 colocalized with CADM1, Lin7, CASK, GluN1, and M-cadherin.
  • MPP2 formed a molecular complex with CADM1, CASK, M-cadherin, and Lin7.
  • MPP2 deficiency altered Lin7 distribution within CG, indicating its role in synaptic organization.

Conclusions:

  • MPP2 is localized to the excitatory postsynaptic region and adherens junctions in cerebellar granule cells.
  • MPP2 forms a complex with several key synaptic proteins, including CADM1, CASK, M-cadherin, and Lin7.
  • MPP2 plays a significant role in regulating the synaptic distribution of Lin7 at postsynaptic sites in the cerebellum.

Related Concept Videos

Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.6K
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.9K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.8K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.9K
Fusion of Secretory Vesicles with the Plasma Membrane01:26

Fusion of Secretory Vesicles with the Plasma Membrane

Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.4K