CAMSAP2

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CAMSAP2
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000118200

ENSMUSG00000041570

UniProt

Q08AD1

Q8C1B1

RefSeq (mRNA)

NM_001297707
NM_001297708
NM_203459
NM_001389638

NM_001081360
NM_001347109
NM_001347110

RefSeq (protein)

NP_001284636
NP_001284637
NP_982284

NP_001334038
NP_001334039

Location (UCSC)Chr 1: 200.74 – 200.86 MbChr 1: 136.2 – 136.27 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) is a protein that, in humans, is encoded by the CAMSAP2 gene.[5] CAMSAP2 possesses a microtubule-binding domain near the C-terminal region where said microtubule interactions occur. On these C-terminal regions, protein-protein interactions are accelerated by three coiled-coil domains, which function as molecular spacers.[6] CAMSAP2 acts as a microtubule minus-end anchor and binds microtubules through its CKK domain. CAMSAP2 is necessary for the proper organization and stabilization of interphase microtubules. The protein also plays a vital role in cell migration.[7] CAMSAP2 can stabilize and attach microtubule minus ends to the Golgi through the AKAP9 complex and myomegalin. CLASP1 proteins responsible for microtubule stability are not required for the Golgi tethering. When no centromeres are present, AKAP9 and CAMSAP-2 dependent pathways of these microtubule minus ends become a dominant force and must exist in order to observe the maintenance of microtubule density.[8]

3D rendering of the CAMSAP2 protein.[9][10][11]

Structure

Microtubules are cytoskeletal polymers with structurally and functionally different ends. There exists a plus-end and a minus-end on each microtubule. The CAMSAP family of proteins contributes to regulating the minus-ends of microtubules.[12] CAMSAP2 contains a CKK domain that binds to microtubules. This CKK domain is a defining factor of the CAMSAP protein family. It enables CAMSAP2 to recognize and bind to microtubule minus ends and allows CAMSAP2 to decorate and stabilize the microtubule lattice formed by minus-end polymerization.[13] In addition to a CKK domain, CAMSAP2 contains an N-terminal calponin homology domain involved with actin binding.[14]

Function

Non-centrosomal microtubule maintenance

CAMSAP2 proteins are observed to be primarily responsible for the maintenance of non-centrosomal microtubules. In epithelial cells, major microtubules are not anchored to the centrosome, which can be observed in other cell types. CAMSAP2 cooperates with calmodulin-regulated spectrin-associated protein 3 (CAMSAP3) to achieve the organization observed in these non-centrosomal microtubules. They possess the ability to suppress the organization of microtubules by the centrosome, and this family of proteins is important for the suitable arrangement of organelles in the cell body. These proteins gathered at the minus ends of these non-centrosomal microtubules can stabilize them. Without these proteins, the Golgi apparatus would exhibit irregular distributions of the microtubules.[15]

Pancreatic islet cells

In pancreatic β-cells, glucose stimulation leads to the remodeling of microtubules responsible for insulin secretion. CAMSAP2 binds to the minus ends of microtubules in normal clonal cells. The knockdown of CAMSAP2 in these β-cells reduces the total insulin content secreted through glucose-stimulated insulin secretion. However, CAMSAP2 localizes to the Golgi apparatus instead of the microtubule minus ends. This oddity is observed only in β-cells as opposed to α-cells. With this collection at the Golgi apparatus, CAMSAP2 promotes the protein trafficking of the Golgi, efficiently facilitating the process. Without CAMSAP2, there would not be adequate insulin production for secretion from these β-cells.[16]

Migration

CAMSAP2-dependent microtubule organization promotes directional

cell polarization because the stretches of CAMSAP2-decorated microtubules enable proper microtubule organization to achieve spatial redistribution and functional specialization of components in the cell. In wound healing assays, CAMSAP2 depletion reduced the ability of cells to close a wound, indicating impaired directional migration.[17] CAMSAP2 populates the cytoplasm with microtubules, allowing the cell to regenerate its cytoskeleton
and facilitate effective cell migration.

Microtubule nucleation

Nucleation and aster formation activity of CAMSAP2. Observe the microtubule projections from the black dots (CAMSAP2 complexes).[18]

The initial polymerization of microtubules can be called

γ-tubulin ring complex is recruited to facilitate the nucleation process; however, CAMSAP2 can act as a strong nucleating agent for microtubule formation independent of this γ-tubulin. CAMSAP2 significantly reduces the nucleation energy barrier by stabilizing longitudinal interactions between the αβ-tubulin dimers, thereby increasing the critical concentration for nucleation. CAMSAP2 achieves this increase by clustering with the αβ-tubulin dimers to generate intermediates from which multiple microtubules can originate, promoting new astral microtubule growth.[19]

Regulation

Regulator of neuronal polarity and development

CAMSAP2 is responsible for controlling

MTOC). This phenomenon sees the existence of free minus and plus-ends throughout the cell. As stated previously, CAMSAP2 has an affinity for binding to free microtubule minus ends in the cell. The stabilization CAMSAP2 can achieve by binding to the free ends of these microtubules is quite important in regulating neuronal polarity. These highly polarized neurons are formed in the developing neocortex, and the centrosome loses its function as an MTOC. CAMSAP2 structures' stability-providing qualities ensure the fate of the axon and the development of neuronal polarity needed for neocortex development. Neurons lacking CAMSAP2 fail to begin axon formation and lack neuronal polarization.[20]

Regulator of blood–testis barrier (BTB)

CAMSAP2 is involved in targeting microtubule minus-ends in

actin filaments caused by the injury, enabling proper distribution of BTB-associated proteins at the cell junctions.[21]

Clinical research

Hepatocellular carcinoma (HCC)

CAMSAP2 plays a significant role in the migration of cancer cells. It has been observed that CAMSAP2 is severely upregulated in cancers such as

c-Jun transrepression of HDAC6 along the Trio-dependent Rac1/JNK pathway, inhibiting CAMSAP2-mediated HCC metastasis.[22]

Colorectal cancer

CAMPSAP promotes the migration of colorectal cancer cells by activating the

MMP-1, regulated the invasion of these cells and slowed down disease progress. Metastasis of this cancer permeates through the activation of this signaling pathway and indicates CAMSAP2 as a promising target for treating metastatic colorectal cancer patients.[23]

Gastric cancer

An association between CAMSAP2 expression levels and the progression and prognosis of gastric cancer was investigated in 2023.

E-cadherin. The high expression of CAMSAP2 contributes to gastric cancer progression and poor prognosis by the upregulation of TGF-β signaling.[24]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118200 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041570 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "CAMSAP2 calmodulin regulated spectrin associated protein family member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2024-02-27. Retrieved 2024-03-11.
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  9. ^ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Archived from the original on 2022-10-01. Retrieved 2024-04-12.
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  13. ^ "UniProt". www.uniprot.org. Archived from the original on 2024-04-15. Retrieved 2024-04-14.
  14. PMID 24486153. Archived
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  17. PMID 24486153. Archived
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  20. PMID 24908486. Archived
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  21. ^
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  25. PMID 21295093
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Further reading

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