Rab1a regulates sorting of early endocytic vesicles

We previously reported that Rab1a is associated with asialoorosomucoid (ASOR)-containing early endocytic vesicles, where it is required for their microtubule-based motility. In Rab1a knockdown (KD) cell lines, ASOR failed to segregate from its receptor and, consequently, did not reach lysosomes for degradation, indicating a defect in early endosome sorting. Although Rab1 is required for Golgi/endoplasmic reticulum trafficking, this process was unaffected, likely due to retained expression of Rab1b in these cells. The present study shows that Rab1a has a more general role in endocytic vesicle processing that extends to EGF and transferrin (Tfn) trafficking. Compared with results in control Huh7 cells, EGF accumulated in aggregates within Rab1a KD cells, failing to reach lysosomal compartments. Tfn, a prototypical example of recycling cargo, accumulated in a Rab11-mediated slow-recycling compartment in Rab1a KD cells, in contrast to control cells, which sort Tfn into a fast-recycling Rab4 compartment. These data indicate that Rab1a is an important regulator of early endosome sorting for multiple cargo species. The effectors and accessory proteins recruited by Rab1a to early endocytic vesicles include the minus-end-directed kinesin motor KifC1, while others remain to be discovered.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:306

Enthalten in:

American journal of physiology. Gastrointestinal and liver physiology - 306(2014), 5 vom: 01. März, Seite G412-24

Sprache:

Englisch

Beteiligte Personen:

Mukhopadhyay, Aparna [VerfasserIn]
Quiroz, Jose A [VerfasserIn]
Wolkoff, Allan W [VerfasserIn]

Links:

Volltext

Themen:

37281-36-0
Asialoglycoproteins
Asialoovomucoid
EC 3.6.4.4
EC 3.6.5.2
EGF
Endocytosis
Journal Article
KIFC1 protein, human
Kinesins
Ovomucin
Rab1 GTP-Binding Proteins
Rab1a
Research Support, N.I.H., Extramural
Sorting
Transferrin

Anmerkungen:

Date Completed 24.04.2014

Date Revised 03.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1152/ajpgi.00118.2013

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM234322322