8.A.109. The Endoplasmic Reticulum Junction-forming protein (Lunapark) Family 

Lnp1p, a member of the conserved Lunapark family, plays a role in ER network formation in yeast. Lnp1p binds to the reticulons and Yop1p and resides at ER tubule junctions in both yeast and mammalian cells. In the yeast Saccharomyces cerevisiae, the interaction of Lnp1p with the reticulon protein, Rtn1p, and the localization of Lnp1p to ER junctions are regulated by Sey1p, the yeast orthologue of atlastin. Chen et al. 2012 proposed that Lnp1p and Sey1p act antagonistically to balance polygonal network formation. In support of this proposal, they showed that the collapsed, densely reticulated ER network in lnp1 Δ cells is partially restored when the GTPase activity of Sey1p is abrogated.

Mammalian Lnp1 (mLnp1) affects ER junction mobility and hence network dynamics. Three-way junctions with mLnp1 are less mobile than junctions without mLnp1. Newly formed junctions that acquire mLnp1 remain stable within the ER network, whereas nascent junctions that fail to acquire mLnp1 undergo rapid ring closure. Thus, mLnp1 plays a key role in stabilizing nascent three-way ER junctions (Chen et al. 2015). Moreover, Lnp1 maintains nucleopore stability and plays a role in NPC integrity, separate from its functions in the ER. It may be linked to Ndc1 and Rtn1 interactions (Casey et al. 2015). In plants (A. thaliana), AtLNP1 and AtLNP2 are involved in determining the network morphology of the plant ER, possibly by regulating the formation of ER cisternae (Kriechbaumer et al. 2018).


 

References:

Casey, A.K., S. Chen, P. Novick, S. Ferro-Novick, and S.R. Wente. (2015). Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum. Mol. Biol. Cell 26: 2833-2844.

Chen, S., P. Novick, and S. Ferro-Novick. (2012). ER network formation requires a balance of the dynamin-like GTPase Sey1p and the Lunapark family member Lnp1p. Nat. Cell Biol. 14: 707-716.

Chen, S., T. Desai, J.A. McNew, P. Gerard, P.J. Novick, and S. Ferro-Novick. (2015). Lunapark stabilizes nascent three-way junctions in the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 112: 418-423.

Choi, H., Y.C. Liao, Y.J. Yoon, J. Grimm, L.D. Lavis, R.H. Singer, and J. Lippincott-Schwartz. (2023). Lysosomal release of amino acids at ER three-way junctions regulates transmembrane and secretory protein mRNA translation. bioRxiv.

Hoyer, M.J., P.J. Chitwood, C.C. Ebmeier, J.F. Striepen, R.Z. Qi, W.M. Old, and G.K. Voeltz. (2018). A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission. Cell 175: 254-265.e14.

Kriechbaumer, V., E. Breeze, C. Pain, F. Tolmie, L. Frigerio, and C. Hawes. (2018). Arabidopsis Lunapark proteins are involved in ER cisternae formation. New Phytol 219: 990-1004.

Examples:

TC#NameOrganismal TypeExample
8.A.109.1.1

The ER junction-forming protein, Lunapark, LNP1 of 278 aas and possibly 2 N-terminal TMSs or 4 TMSs in a 2 + 2 arrangement with two N-terminal and 2 more C-terminal (Chen et al. 2012).  LNP1 aids in membrane fusion and maintenance of the endoplasmic reticulum (Casey et al. 2015). Works in conjunction with the ER shaping proteins (reticulons RTN1 and RTN2 (TC# 8.A.102), YOP1), and in antagonism to SEY1 to maintain the network in a dynamic equilibrium. May counterbalance SEY1-directed polygon formation by promoting polygon loss through ring closure (Chen et al. 2012).

LNP1 of Saccharomyces cerevisiae

 
8.A.109.1.2

Uncharacterized zinc_ribbon_10 domain-containing protein of 266 aas and 2 TM

UP of Cyberlindnera jadinii (Torula yeast) (Candida utilis)

 
8.A.109.1.3

Uncharacterized protein of 266 aas and 2 TMSs

UP of Aspergillus candidus

 
8.A.109.1.4

Uncharacterized protein of 378 aas and 2 TMSs

UP of Diplocarpon rosae

 
8.A.109.1.5

The Endoplasmic Reticular (ER) three way tubular junctions, consisting of three known proteins, TMCC3, Atlastin-2 and Lunapark (Wisesa et al. 2019). See family description for details regarding TMCC3. Atlastin-2 is a GTPase, tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of ER membranes. It functions in ER tubular network biogenesis (Hu et al. 2009, Wang et al. 2016). Lunapark (LNPK, LNP), with 2 TMSs, is an ER-shaping membrane protein that plays a role in determining ER morphology (Breuss et al. 2018). It is involved in the stabilization of nascent three-way ER tubular junctions within the ER network (Moriya et al. 2013, Shemesh et al. 2014, Chen et al. 2015, Wang et al. 2016). It may also play a role as a curvature-stabilizing protein within the three-way ER tubular junction network (Shemesh et al. 2014). It may also be involved in limb development as well as central nervous system development (Breuss et al. 2018). A longer homolog (see TC# 8.A.1109.1.6) with 653 aas and 2 C-terminal TMSs (TMCC1). TMCC1 is upregulated in gliomas, and its overexpression indicates a poor prognosis for disease oucome. Knockdown of TMCC1 inhibited cell proliferation and induced apoptosis. TMCC1 induces cell migration and invasion by promoting the epithelial-mesenchymal transition (EMT) (Gao et al. 2022). Translation of secretome mRNAs occurs preferentially near lysosomes on ER marked by the ER junction-associated protein, Lunapark. Knockdown of Lunapark reduces the extent of secretome mRNA translation without affecting translation of other mRNAs (Choi et al. 2023).

 

The ER-TJ complex of Homo sapiens,
consisting of:
TMCC3, 477 aas with 2 C-terminal TMSs, Q9ULS5.
Atlastin-2, 583 aas with two C-terminal TMSs, Q8NHH9; see family 1.G.5.
Lunapark, 428 aas with two N-terminal TMSs, Q9C0E8; see family 8.A.109.

 
8.A.109.1.6

TMCC1 (Transmembrane and coiled-coil domains protein 1) of 653 aas and 2 C-terminal TMSs. It is 52% similar to Lunapark of 428 aas and 2 TMSs near the N-terminus of the protein. It is an ER membrane protein that promotesER-associated endosome fission and localizes to contact sites between the endoplasmic reticulum and endosomes to promote recruitment of the ER to endosome tubules for fission (Hoyer et al. 2018).Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane.

TMCC1 of Homo sapiens

 
Examples:

TC#NameOrganismal TypeExample
8.A.109.2.1

Lunapark LNP1 of 408 aas and 2 N-terminal TMSs. Kriechbaumer et al. 2018 identified two Arabidopsis LNP homologues and investigated their subcellular localization via confocal microscopy and potential function in shaping the ER network using protein-protein interaction assays and mutant analysis. They showed that AtLNP1 overexpression in tobacco leaf epidermal cells mainly labels cisternae in the ER network, whereas AtLNP2 labels the whole ER. Overexpression of LNP proteins resulted in an increased abundance of ER cisternae. AtLNP1 and AtLNP2 appear to be involved in determining the network morphology of the plant ER, possibly by regulating the formation of ER cisternae (Kriechbaumer et al. 2018).

LNP1 of Arabidopsis thaliana

 
8.A.109.2.2

At LNP2 of 409 aas and 2 N-terminal TMSs (Kriechbaumer et al. 2018).

LNP2 of Arabidopsis thaliana (Mouse-ear cress)