1.A.64 The Plasmolipin (Plasmolipin) Family
Plasmolipin (PLLP) is an 18-kDa proteolipid or lipoprotein found in kidney and brain, where it is restricted to the apical surface of tubular epithelial cells and to mammalian myelinated tracts, respectively. This protein is made during sciatic nerve development and regeneration in the rat. It has 182 aas and 4 TMSs (Fischer and Sapirstein, 1994). Addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K+-selective (Tosteson and Sapirstein, 1981). PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex (Yaffe et al. 2015).
Plasmolipin has many homologues. These are referred to as CKLF-like MARVEL transmembrane domain containing protein, chemokine-like factor and T-cell differentiation marker (Mitsugumin and Synaptogyrin). Most are about 180 residues, but several are about twice as large with 8 TMSs and an internal repeat (e.g., the myeloid-associated differentiation marker of humans (MAL or MYADM; Q96S97) or the rat (EAL84950). Synthesis of these proteins are induced by retinoic acid (Cui et al., 2001).
Plasmolipin localizes to and recycles between the plasma membrane and the Golgi complex. In the Golgi complex, it forms oligomers which block Golgi to plasma membrane transport of the secretory vesicular stomatitis virus G protein (VSVG) (Yaffe et al. 2015).
The transport reaction that occurs with plasmolipin in artificial membranes is:
Ions (in) Ions (out)
Myelin and Lymphocyte Protein, MAL/VIP17 protein, a regulator of NKCC2 (2.A.30.1.1). It stabilizes kidney apical membranes, and facilitates sorting of proteins to these membranes (Carmosino et al., 2010). Like plasmolipin, it has 4 TMSs that align with those of plasmolipin.
MAL/VIP17 of Canis familiaris (Q28296)
Myeloid-associated differentiation marker, MyADM (322 aas; 8 TMSs)
MyADM of Homo sapiens (Q96S97)
4 TMS MARVEL superfamily member
4TMS homologue of Caenorhabditis elegans (P83387)
CKLF-like MARVEL transmembrane domain-containing protein 7, CMTM7 (175aas; 4 TMSs; Miyazaki et al., 2012). CMTM7 functions to link sIgM and BLNK in the plasma membrane, to recruit BLNK to the vicinity of Syk, and to initiate BLNK-mediated signal transduction (Miyazaki et al., 2012). No transport function is known.
CMTM7 of Homo sapiens (Q96FZ5)
Proteolipid protein 2 (Differentiation-dependent protein A4) (Intestinal membrane A4 protein)
A4 protein of Homo sapiens
Uncharacterized protein of 208 aas
UP of Caenorhabditis elegans
CKLF-like MARVEL transmembrane domain-containing protein 8 of 343 aas and 4 TMSs, CMTM8. A short splice variant, CMTM8-v2, retains the ability to induce apoptosis via caspase-dependent and -independent pathways to inhibit cell growth and colony formation. CMTM8 and CMTM8-v2 display different expression profiles and distinct subcellular localization patterns, while operating via different mechanisms to induce apoptosis. CMTM8-v2 does not affect EGFR internalization, implying that the MARVEL domain and/or the cytosolic YXXPhi motifs are necessary for CMTM8 to accelerate ligand-induced EGFR internalization (Li et al. 2007).
CMTM8 of Anas platyrhynchos (Mallard) (Anas boschas)
CKIF-like MARVEL transmembrane domain containing protein 1 of 169 aas and 4 TMSs, CMTM1.
CMTM1 of Homo sapiens
Marvel D3 tight junctionh-associated occludin of 401 aas and 4 TMSs; a determinant of paracellular permeability (Steed et al. 2009).
MarvelD3 of Homo sapiens