Eylem Seç
LRP1 Endocytosis is Regulated by KIF13B through the Interaction with hDLG1
Başlık:
LRP1 Endocytosis is Regulated by KIF13B through the Interaction with hDLG1
Yazar:
Mills, Joslyn E., author.
ISBN:
9780438031036
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (69 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Laura Liscum; Athar Chishti Committee members: Brent Cochran; Ronald Dubreuil; Peter Juo.
Özet:
KIF13B, a kinesin-3 family motor, was originally identified by virtue of its biochemical interaction with human homolog of Drosophila discs large tumor suppressor (hDLG1). Unlike its homolog KIF13A, the KIF13B contains a carboxyl-terminal CAP-Gly domain. To investigate the specific functional role of the CAP-Gly domain in KIF13B, and its possible compensation by KIF13A, we developed two mouse models. One mouse model expresses a truncated form of KIF13B protein lacking only its CAP-Gly domain (KIF13BDeltaCG), whereas the second model lacks the full-length KIF13A (KIF13A FLKO). Using these mouse models, we show that the KKIF13BDeltaCG mice exhibit relatively higher levels of serum cholesterol consistent with the reduced uptake of [ 3H]CO-LDL in KKIF13BDeltaCG mouse embryo fibroblasts. In contrast, the serum level of factor VIII was not significantly elevated in the KKIF13BDeltaCG as compared to wild-type mice, suggesting that the CAP-Gly domain of KIF13B selectively regulates Low density lipoprotein Related Protein 1-mediated lipoprotein endocytosis. No elevation of either serum cholesterol or factor VIII was observed in the KIF13A FLKO. Moreover, we found that the deletion of the CAP-Gly domain caused subcellular mislocalization of truncated KIF13B with concomitant mislocalization of LRP1. To further delineate the biochemical basis of the LRP1-KIF13B complex at the plasma membrane, we discovered that the cytoplasmic domain of LRP1 interacts specifically with the alternatively spliced I3 domain of hDLG1, which in turn recognizes the MBS domain of KIF13B. Together, this study provides evidence for the biochemical basis of LRP1-hDlg1-KIF13B complex formation, which regulates LRP1-mediated interactions with implications in metabolism, cell polarity, and development.
Notlar:
School code: 0845
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(678467.1) | 678467-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.