9.B.135 The Membrane Trafficking Yip (Yip) Family

The YIP1 family of proteins are small membrane proteins with 5 putative TMSs with roles in membrane trafficking from the ER to the golgi. In yeast they participate in vesicle biogenesis and mediate the association of Rab proteins with membranes. Yeast YIP1 is an essential gene and can be fully complemented by a human counterpart, suggesting that the essential function of Yip1p is evolutionarily conserved (Chen and Collins, 2005).  Prokaryotic homologues are found in family 9.B.29, and families 9.B.29 and 9.B.135 may comprise a superfamily.

Human YIPF3 and YIPF4 are localized to the cis-Golgi. YIPF3 is synthesized in the ER as a N-glycosylated form (40 kDa), is then O-glycosylated in the Golgi and finally is cleaved at its C-terminal luminal domain. YIPF3 and YIPF4 form a complex in the Golgi apparatus. The knockdown of YIPF3 or YIPF4 in HeLa cells induced fragmentation of the Golgi apparatus (Tanimoto et al., 2011). Mutation of Yip1 domain family, member 6 (Yipf6), induces spontaneous intestinal inflammation in mice (Brandl et al., 2012). YIPF proteins primarily localise to the Golgi complex and can be grouped into trans-Golgi-localising YIPFs (YIPF1 and YIPF2) and cis-Golgi-localising YIPFs (YIPF3, YIPF4 and YIPF5), with YIPF6 and YIPF7 showing a broader profile being distributed throughout the Golgi stack (Kranjc et al. 2017). YIPF proteins have a long soluble N-terminal region, which is orientated towards the cytosol, followed by 5 closely stacked TMSs, and a C terminus, orientated towards the lumen of the Golgi. A number of specific morphological changes to this organelle on their depletion (Kranjc et al. 2017). Transcriptional regulation analysis of porcine Yip1 domain family member 3 genehas been reported (Ni et al. 2020).

S. cerevisiae contains four YIPFs: Yip1p, Yif1p, Yip4p, and Yip5p. Yip1p and Yif1p bind to each other and play a role in budding of transport vesicles and/or fusion of vesicles to target membranes. Human cells have nine family members that have overlapping functions. These YIPF proteins are divided into two sub-families: YIPFα/Yip1p and YIPFβ/Yif1p. A YIPFα molecule forms a complex with a specific partner YIPFβ molecule. A basic tetrameric complex is formed from two molecules of each partner YIPF protein, and this tetramer forms a higher order oligomer (Shaik et al. 2019). Three distinct YIPF protein complexes are formed from pairs of YIPFα and YIPFβ proteins. These are differently localized in either the early, middle, or late compartments of the Golgi apparatus and are recycled between adjacent compartments. Because a YIPF protein is predicted to have five TMSs, a YIPF tetramer complex is predicted to have 20 TMSs. This high number of TMSs suggests that YIPF complexes function as channels, transporters, or transmembrane receptors (Shaik et al. 2019).

The degradation of organelles by autophagy is essential for cellular homeostasis. The Golgi apparatus has been shown to be degraded by autophagy. Kitta et al. 2024 found that the five-pass transmembrane Golgi-resident proteins YIPF3 and YIPF4 constitute a Golgiphagy receptor. The interaction of this complex with LC3B, GABARAP, and GABARAPL1 is dependent on a LIR motif within YIPF3 and putative phosphorylation sites immediately upstream; the stability of the complex is governed by YIPF4. Expression of a YIPF3 protein containing a mutated LIR motif caused an elongated Golgi morphology, indicating the importance of Golgi turnover via selective autophagy (Kitta et al. 2024). 

References: