A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

Abstract

During the preparation of this manuscript, one of Kathrin N. Karle's affiliations was inadvertently omitted. The correct affiliation list is above. In addition, information was omitted from the Acknowledgments section. The correct Acknowledgments section is below. We thank M. Öhler, B. Schade, K. Schorr, A. Büschel, K. Stein, and R. Kaiser for their excellent technical assistance. We thank Nadine Breitkreutz for excellent technical analyses. We thank C. Kaether for valuable discussions and Laura McMillan for editing the final manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) to M.M. Kessels (KE685/3-1), B. Qualmann (QU116/6-1), C. Beetz (BE4069/1-1), T. Deufel and C.A. Hübner (DE307/8-1), and C.A. Hübner (HU800/6-1). The work of Kathrin N. Karle was supported by the German Ministry of Education and Research (BMBF) through funding to the mitoNET (01GM1113E).

Cooperative functions of the two F-BAR proteins Cip4 and Nostrin in regulating E-cadherin in epithelial morphogenesis

“…Freeze-fracturing of liposomes incubated with proteins (1.7 mM) was done according to Beetz et al, 2013. Immunolabeling of freeze-fracture replica was adapted from procedures we have recently developed in order to visualize proteins of the syndapin F-BAR-domain protein subfamily at freeze-fractured membranes of cells and brain tissues (Koch et al, 2012a;Schneider et al, 2014), by using rabbit anti-GST antibodies (Qualmann et al, 1999;1:100) and 10 nm gold-conjugated goat anti-rabbit IgGs (British Biocell International; 1:50) in single-labeling experiments.…”

Functional Mutation Analysis Provides Evidence for a Role of REEP1 in Lipid Droplet Biology

“…Mutations in REEP1 (MIM #609139) cause autosomal dominant HSP type 31 (SPG31) [Zuchner et al, 2006] as well as distal hereditary motor neuropathy (dHMN) [Beetz et al, 2012]. The encoded product REEP1 had initially been considered a mitochondrial protein [Zuchner et al, 2006], but was subsequently shown to be targeted to the ER Beetz et al, 2013]. It contains two hydrophobic regions: one at the N-terminus, and one lying more centrally.…”

“…The latter is unusually long for a classical transmembrane stretch and represents the REEP homology domain. It was shown to insert into membranes as a hairpin, to actively bend these membranes, to mediate localization to highly curved ER compartments, and to be responsible for an interaction with structurally similar regions in atlastins, reticulons, and spastin Beetz et al, 2013]. A unique in-frame splice defect underlies dHMN [Beetz et al, 2012], whereas the majority of REEP1 mutations in HSP patients is truncating [Beetz et al, 2008;Goizet et al, 2011].…”

Hereditary spastic paraplegia‐linked REEP1 modulates endoplasmic reticulum/mitochondria contacts

“…1,2,4 Receptor expression enhancing protein 1 (REEP1) is believed to encode an endoplasmic reticulum (ER) protein and mutations are associated with autosomal-dominant HSP (SPG31) as well as distal hereditary motor neuropathy. [5][6][7] There are six members of the REEP proteins, REEP1-6, which can be grouped into two subfamilies, REEP1-4 and REEP5-6, based on structural and sequence homology. They share sequence homology with yeast Yop1 and plant HVA22 protein and all belong to the Yip (Ypt-interacting protein) family.…”

“…Haploinsufficiency or loss of function has been suggested for the underlying molecular genetic mechanism of REEP1 in SPG31. 6,13,16,49 The differences in luciferase activity observed in point mutations and truncated mutations (Fig 7A), prompted us to test whether Reep1 mutations also function in a dominant negative fashion. Thus, we examined whether Reep1 P19R or Reep1 A20E inhibit the function of WT Reep1.…”